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| Profile Name | TP53 - NTRK1 |
| Gene Variant Detail | |
| Relevant Treatment Approaches | Larotrectinib |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 mutant | colorectal cancer | sensitive | PD0166285 | Preclinical | Actionable | In a preclinical study, PD0166285 sensitizes colorectal cancer cells with TP53 mutation to radiation induced cell death (PMID: 11719452). | 11719452 |
| TP53 mutant | Advanced Solid Tumor | sensitive | Bevacizumab | Clinical Study - Cohort | Actionable | In a retrospective study, Avastin (bevacizumab) treatment was associated with increased progression-free survival in cancer patients carrying TP53 mutations (PMID: 23670029). | 23670029 |
| TP53 mutant | medulloblastoma | decreased response | JQ1 | Preclinical | Actionable | In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). | 24231268 |
| TP53 mutant | glioblastoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Adavosertib (MK-1775) and radiation therapy synergized to inhibit tumor growth in a human glioblastoma multiforme cell line xenograft model harboring mutant TP53 (PMID: 21992793). | 21992793 |
| TP53 mutant | head and neck squamous cell carcinoma | sensitive | AZD7762 + Cisplatin | Preclinical | Actionable | In a preclinical study, the treatment of a head and neck squamous cell carcinoma cell line with mutant TP53 (C176F and A161S) with AZD7762, a pan Chk1/2 inhibitor, sensitizes the cells to Platinol (cisplatin) (PMID: 23839309). | 23839309 |
| TP53 mutant | neuroblastoma | resistant | Nutlin-3a | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to nutlin-3 mediated growth inhibition (PMID: 21725357). | 21725357 |
| TP53 mutant | neuroblastoma | resistant | MI-63 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to MI-63 mediated growth inhibition (PMID: 21725357). | 21725357 |
| TP53 mutant | Advanced Solid Tumor | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) improved progression-free survival and overall survival in advanced solid tumor patients harboring TP53 hotspot mutations, and resulted in an increased stable disease rate of 45% (5/11), compared to a stable disease rate of 16% (4/25) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | sarcoma | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| TP53 mutant | colorectal cancer | sensitive | Pazopanib + Vorinostat | Phase I | Actionable | In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). | 25669829 |
| NTRK1 fusion | colorectal cancer | sensitive | AZD7451 | Preclinical | Actionable | In a preclinical study, AZD7451 treatment efficiently inhibited proliferation of a colorectal cancer cell line harboring a NTRK1 fusion in culture (PMID: 25054037). | 25054037 |
| TP53 mutant | lung non-small cell carcinoma | sensitive | CEP-8983 + Cisplatin | Preclinical | Actionable | In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). | 23428903 |
| TP53 mutant | sarcoma | sensitive | Pazopanib | Clinical Study - Cohort | Actionable | In a retrospective analysis, advanced sarcoma patients with TP53 mutations displayed improved progression-free survival (208 vs 136 days, p=0.036) relative to patients with wild-type TP53 when treated with Votrient (pazopanib) (PMID: 26646755). | 26646755 |
| TP53 mutant | leukemia | decreased response | RG7112 | Phase I | Actionable | In a Phase I clinical trial, the majority of 19 leukemia patients with identified TP53 mutations did not demonstrate response to treatment with RG7112, with 2 acute myeloid leukemia patients harboring TP53 mutations showing clinical activity, but not improvement, and 1 sCLL/CLL patient achieving stable disease (PMID: 26459177). | 26459177 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Duvelisib | Phase I | Actionable | In a Phase I trial, Copiktra (duvelisib) treatment inhibited Akt phosphorylation, resulted in complete response in 2% (1/49), partial response in 53% (26/49), and stable disease in 43% (21/49) of chronic lymphocytic leukemia patients, of which 49% (23/47) carried TP53 mutations (Blood 124 (21): 3334). | detail... |
| TP53 mutant | ovarian clear cell adenocarcinoma | decreased response | DS-7423 | Preclinical | Actionable | In a preclinical study, ovarian clear cell adenocarcinoma cell lines harboring TP53 mutations demonstrated reduced sensitivity to DS-7423 induced apoptosis in culture compared to TP53 wild-type cells (PMID: 24504419). | 24504419 |
| TP53 mutant | neuroblastoma | resistant | GSK2830371 | Preclinical | Actionable | In a preclinical study, neuroblastoma cell lines harboring TP53 mutations were resistant to GSK2830371 induced growth inhibition in culture (PMID: 25658463). | 25658463 |
| TP53 mutant | Advanced Solid Tumor | sensitive | CTX-1 | Preclinical | Actionable | In a preclinical study, CTX-1 induced increased Tp53 protein levels and cell death in human tumor cell lines with mutant Tp53 in culture (PMID: 26883273). | 26883273 |
| TP53 mutant | colorectal cancer | sensitive | Prodigiosin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 26759239). | 26759239 |
| TP53 mutant | ovarian cancer | no benefit | Nutlin-3a | Preclinical | Actionable | In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with TP53 mutations in culture (PMID: 25964101). | 25964101 |
| TP53 mutant | ovarian cancer | sensitive | Etoposide + Nutlin-3a | Preclinical | Actionable | In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). | 25964101 |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Larotrectinib | FDA approved | Actionable | In three trials that supported FDA approval, Vitrakvi (larotrectinib) treatment resulted in an overall response rate of 75% (41/55) in adult and pediatric patients with advanced solid tumors harboring either an NTRK1, NTRK2, or NTRK3 fusion, including 7 patients achieving a complete response and 34 patients achieving a partial response (PMID: 29466156; NCT02122913, NCT02637687, NCT02576431). | detail... 29466156 detail... |
| NTRK1 rearrange | Advanced Solid Tumor | predicted - sensitive | Entrectinib | Clinical Study | Actionable | In a clinical study, Rozlytrek (entrectinib) treatment resulted in objective response in 75% (3/4) of patients with advanced solid tumors harboring rearrangement in NTRK1, NTRK2, or NTRK3 genes (AACR Apr 2016, Abstract # CT007). | detail... |
| TP53 mutant | glioblastoma | sensitive | Adavosertib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Adavosertib (MK-1775) decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). | 27196784 |
| TP53 mutant | hypopharynx cancer | resistant | unspecified EGFR antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of two unspecified EGFR antibodies targeting nonoverlapping epitopes of Egfr did not inhibit proliferation of Tp53 mutated hypopharyngeal carcinoma cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Erbb3 (Her3) antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Igf-1r antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | hypopharynx cancer | predicted - sensitive | unspecified EGFR antibody + unspecified ERBB3 antibody + unspecified IGF-1R antibody | Preclinical - Cell culture | Actionable | In a preclinical study, combination of an unspecified EGFR antibody, an unspecified Erbb3 (Her3) antibody, and an unspecified Igf-1r antibody resulted in potent inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). | 27196767 |
| TP53 mutant | Advanced Solid Tumor | resistant | KRT-232 | Preclinical - Cell culture | Actionable | In a preclinical study, KRT-232 (AMG 232) did not inhibit growth of human tumor cell lines harboring TP53 mutations in culture (PMID: 25567130). | 25567130 |
| TP53 mutant | colorectal cancer | predicted - sensitive | NSC59984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NSC59984 treatment resulted in increased Tp53 signaling and cell death in colorectal cancer cell lines harboring TP53 mutations, and inhibited tumor growth in TP53-mutant cell line colorectal cancer xenograft models (PMID: 26294215). | 26294215 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Carboplatin + Nutlin-3a | Preclinical - Cell culture | Actionable | In a preclinical study, Nutlin-3 and Paraplatin (carboplatin) synergistically inhibited growth in TP53 mutated triple-receptor negative breast cancer cell lines in culture and in cell line xenograft models (PMID: 26494859). | 26494859 |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a retrospective analysis of a Phase I trial, Adavosertib (MK-1775) combined with a chemotherapy resulted in a 21% (4/19) response rate in advanced solid tumor patients harboring a TP53 mutation and in those without a TP53 mutation, a 12% (4/33) response rate was observed (PMID: 27601554; NCT00648648). | 27601554 |
| TP53 mutant | tongue squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a tongue squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 mutant | pharynx squamous cell carcinoma | sensitive | Ceralasertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a pharynx squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). | 28062704 |
| TP53 mutant | ovarian serous carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment decreased mutant Tp53 level, resulted in apoptosis of ovarian serous carcinoma cells harboring TP53 mutations in culture (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | Doxorubicin + Seliciclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-mutant triple-receptor negative breast cancer cell lines in culture, and inhibited tumor growth, prolonged survival in cell line xenograft models (PMID: 26826118). | 26826118 |
| TP53 mutant | triple-receptor negative breast cancer | predicted - sensitive | GDC-0425 + Gemcitabine | Phase I | Actionable | In a Phase I trial, treatment with GDC-0425 followed by Gemzar (gemcitabine) resulted in a partial response in a patient with triple-receptor negative breast cancer harboring a TP53 mutation (PMID: 27815358). | 27815358 |
| TP53 mutant | breast cancer | sensitive | PK11007 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53-mutated breast cancer cell lines demonstrated increased sensitivity to PK11007 compared to TP53-wild type cells in culture, regardless of Esr1 and Erbb2 (Her2) status (J Clin Oncol 35, 2017 (suppl; abstr e14099)). | detail... |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, a retrospective analysis of a Phase I trial demonstrated non-small cell lung carcinoma (NSCLC) patients harboring either a TP53 mutation (n=15) or KRAS mutation (n=8) had greater progression free survival compared to NSCLC patients harboring wild-type TP53 or KRAS (n=15) (14.5mo vs 14.7mo vs 3.5mo, respectively) when treated with Keytruda (pembrolizumab) (PMID: 28039262). | 28039262 |
| TP53 mutant | ovarian cancer | predicted - sensitive | Adavosertib + Carboplatin | Phase II | Actionable | In a Phase II trial, Paraplatin (carboplatin) and Adavosertib (MK-1775) combination treatment resulted in an overall response rate of 43% (9/21), a median progression-free survival of 5.3 months and a median overall survival of 12.6 months in ovarian cancer patients harboring TP53 mutations (PMID: 27998224; NCT01164995). | 27998224 |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial, Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy resulted in a response rate of 100% (14/14, 9 complete response, 5 partial response) in relapsed or refractory chronic lymphocytic leukemia (CLL) patients, and a response rate of 100% (16/16, 9 complete response, 7 partial response) in untreated patients with high-risk features including del 17p, TP53 mutations, and del 11q (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 429; NCT02756897). | detail... |
| TP53 mutant | colon carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant colon carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 mutant | breast carcinoma | predicted - sensitive | Camptothecin + CHIR-124 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant breast carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). | 17255282 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is included in guidelines as first-line therapy (category 2A) and second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Rituximab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Rituxan (rituximab) is included in guidelines as second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is included in guidelines as second-line or subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | TP53 mutations except P47S and P72R are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with inferior leukemia-free survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| TP53 mutant | medulloblastoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with aggressive disease in patients with SHH-activated medulloblastoma (NCCN.org). | detail... |
| TP53 mutant | osteosarcoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing osteosarcoma (NCCN.org). | detail... |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Larotrectinib | Phase Ib/II | Actionable | In a Phase I/II trial (SCOUT), Vitrakvi (larotrectinib) treatment resulted in complete response in 26.7% (4/15), partial response in 66.7% (10/15), and stable disease in 6.7% (1/15) of pediatric patients with advanced solid tumors harboring NTRK fusions, and progressive diseases in all 7 patients without NTRK fusions (PMID: 29606586; NCT02637687). | 29606586 |
| TP53 mutant | fibrous histiocytoma | predicted - sensitive | GDC-0575 + Gemcitabine | Preclinical - Pdx | Actionable | In a preclinical study, GDC-0575 and Gemzar (gemcitabine) combination treatment inhibited tumor growth, prolonged progression-free survival in patient-derived xenograft (PDX) models of undifferentiated pleomorphic sarcoma (fibrous histiocytoma) (PMID: 29409053). | 29409053 |
| TP53 mutant | sarcoma | predicted - sensitive | GDC-0575 + Gemcitabine | Phase I | Actionable | In a Phase I trial, GDC-0575 and Gemzar (gemcitabine) combination treatment resulted in a prolonged tumor response in 2 soft tissue sarcoma patients harboring TP53 mutations, and no response in a patient with TP53 wild-type tumor (PMID: 29409053; NCT01564251). | 29409053 |
| TP53 mutant | head and neck squamous cell carcinoma | predicted - sensitive | Buparlisib + Paclitaxel | Phase II | Actionable | In a Phase II (BERIL-1) trial, Buparlisib (BKM120) and Taxol (paclitaxel) combination treatment resulted in improved overall survival (HR=0.52) and prolonged progression-free survival (HR=0.45) in head and neck squamous cell carcinoma patients harboring TP53 mutations compared to TP53 wild-type patients (PMID: 29490986; NCT01852292). | 29490986 |
| TP53 mutant | glioblastoma | sensitive | AZD1390 | Preclinical - Cell culture | Actionable | In a preclinical study, TP53 mutant glioblastoma cells demonstrated increased sensitivity to radiosensitization by AZD1390 treatment compared to TP53 wild-type cells in culture (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). | detail... |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Repotrectinib | FDA approved | Actionable | In a Phase I/II (TRIDENT-1) trial that supported FDA approval, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 58% (23/40), a 12-mo duration of response (DOR) of 86%, and 12-mo progression-free survival (PFS) of 56% in TKI-naive patients with advanced solid tumors harboring NTRK fusions, and a 50% (24/48) cORR, 39% 12-mo DOR, and 22% 12-mo PFS in TKI-pretreated patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116). | detail... detail... |
| NTRK1 fusion | gastrointestinal system cancer | predicted - sensitive | Larotrectinib | Phase I | Actionable | In a combined analysis of 3 clinical trials, Vitrakvi (larotrectinib) treatment resulted in an objective response rate of 75% (8/12, 1 complete response, 7 partial responses) in patients with gastrointestinal system malignancies harboring NTRK fusions, including colon cancer, pancreatic carcinoma, cholangiocarcinoma and GIST, and stable disease in 3 patients, with duration of response ranging from 3.5 to 22.9 months (Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). | detail... |
| NTRK1 fusion | cholangiocarcinoma | sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a combined analysis of 3 clinical trials, Vitrakvi (larotrectinib) treatment resulted in partial response in a patient with cholangiocarcinoma harboring NTRK1 fusion (Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). | detail... |
| NTRK1 fusion | colon cancer | sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a combined analysis of 3 clinical trials, Vitrakvi (larotrectinib) treatment resulted in partial response in 50% (2/4) and stable disease in 50% (2/4) of patients with colon cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). | 29466156 detail... |
| NTRK1 fusion | appendix cancer | predicted - sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a combined analysis of 3 clinical trials, Vitrakvi (larotrectinib) treatment resulted in stable disease in a patient with appendix cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). | 29466156 detail... |
| NTRK1 fusion | pancreatic cancer | sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a combined analysis of 3 clinical trials, Vitrakvi (larotrectinib) treatment resulted in partial response in a patient with pancreatic cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). | 29466156 detail... |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 30% (3/10) of patients with acute myeloid leukemia harboring TP53 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| TP53 mutant | Advanced Solid Tumor | sensitive | unspecified VEGFR inhibitor | Clinical Study - Cohort | Actionable | In a clinical study, VEGF/VEGFR inhibitor treatment resulted in improved rates of response (stable disease over 6 months/partial/complete response, 31% vs 7%), time-to-treatment failure, and overall survival (both p<0.01) compared to control in patients with TP53 mutant advanced solid tumors (n=106), but not in patients with TP53 wild-type tumors (n=82) (PMID: 27466356). | 27466356 |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | CG-806 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring TP53 mutations were sensitive to CG-806 in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1323). | detail... |
| NTRK1 fusion | rectum cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | skin melanoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | Advanced Solid Tumor | predicted - sensitive | Selitrectinib | Phase I | Actionable | In a Phase I trial, Selitrectinib (LOXO-195) treatment resulted in an objective response rate of 34% (10/29) and stable disease in 31% (9/29) of adult and pediatric patients with advanced solid tumors harboring NTRK fusions and had progressed or were intolerant to prior Trk inhibitors (AACR Annual Meeting 2019, Abstract CT127; NCT03215511). | detail... |
| NTRK1 fusion | soft tissue sarcoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic thyroid carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org). | detail... |
| TP53 mutant | acute myeloid leukemia | sensitive | Decitabine | Guideline | Actionable | Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | acute myeloid leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). | detail... |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| TP53 mutant | lung non-small cell carcinoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, immune checkpoint inhibitor treatment including Keytruda (pembrolizumab) (n=1), Opdivo (nivolumab) with (n=8) or without (n=63) Yervoy (ipilimumab) resulted in improved median overall survival (18.1 vs 8.1 months, HR=0.48, p=0.04), median progression-free survival (4.5 vs 1.4 months, p=0.03), and objective response rate (51.2% vs 20.7%, p=0.01) in TP53 mutant (n=41) non-small cell lung cancer patients compared to TP53 wild-type (n=31) patients (PMID: 31097096). | 31097096 |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Entrectinib | FDA approved - On Companion Diagnostic | Actionable | In a combined analysis of 3 clinical trials (ALKA-372-001, STARTRK-1, STARTRK-2) that supported FDA approval, Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (31/54, 4 complete response, 27 partial response) in patients with NTRK1/2/3 fusion-positive advanced solid tumors, with a median duration of response of 10 months (PMID: 31838007; 2012-000148-88, NCT02097810, NCT02568267). | detail... 31838007 |
| NTRK1 fusion | papillary thyroid carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | papillary thyroid carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | follicular thyroid carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | oncocytic carcinoma of the thyroid | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic thyroid carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org). | detail... |
| NTRK1 fusion | follicular thyroid carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | oncocytic carcinoma of the thyroid | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | soft tissue sarcoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | salivary gland cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with NTRK1 fusion-positive salivary gland tumors with distant metastasis (NCCN.org). | detail... |
| NTRK1 fusion | salivary gland cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with NTRK1 fusion-positive salivary gland tumors with distant metastases (NCCN.org). | detail... |
| NTRK1 fusion | ovary epithelial cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | ovary epithelial cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | small intestine adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | colon cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is included in guidelines as first-line (category 2A) and second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Duvelisib | Guideline | Actionable | Copiktra (duvelisib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Phase I | Actionable | In a Phase I trial, Brukinsa (zanubrutinib) treatment resulted in an overall response rate of 100% (16/16) in patients with CLL/SLL harboring del (17p) or TP53 mutations (PMID: 31340982; NCT02343120). | 31340982 |
| NTRK1 fusion | skin melanoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | ovarian cancer | predicted - sensitive | AZD7648 + Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment induced tumor regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| TP53 mutant | ovarian cancer | predicted - sensitive | Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, Lynparza (olaparib) treatment inhibited tumor growth but did not induce regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring wild-type ATM and TP53 mutation (PMID: 31699977). | 31699977 |
| TP53 mutant | ovarian cancer | sensitive | AZD7648 | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of ovarian cancer harboring a TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
| NTRK1 fusion | esophagus adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | gastroesophageal junction adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | esophagus adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | gastroesophageal junction adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | stomach cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | stomach cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | pancreatic adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate, or poor (ECOG 3) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good, intermediate, or poor PS (NCCN.org). | detail... |
| NTRK1 fusion | pancreatic adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease (NCCN.org). | detail... |
| NTRK1 fusion | breast cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | breast cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | cervical cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | cervical cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib + Obinutuzumab | Guideline | Actionable | Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| NTRK1 fusion | hepatocellular carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | hepatocellular carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | gallbladder cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org). | detail... |
| NTRK1 fusion | gallbladder cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org). | detail... |
| NTRK1 fusion | intrahepatic cholangiocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| NTRK1 fusion | intrahepatic cholangiocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| NTRK1 fusion | extrahepatic bile duct carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| NTRK1 fusion | extrahepatic bile duct carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| TP53 mutant | lung non-small cell carcinoma | not predictive | Osimertinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with non-small cell lung cancer harboring TP53 mutations at treatment discontinuation of Tagrisso (osimertinib) had shorter time to treatment discontinuation (6.5 vs 11.5 months, p=0.0029) compared to patients with wild-type TP53 (PMID: 31839416). | 31839416 |
| NTRK1 fusion | endometrial carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | uterine corpus sarcoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | uterine corpus sarcoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | endometrial carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | Advanced Solid Tumor | predicted - sensitive | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a prtial response in 3 and progressive disease in 2 of 6 patients with advanced solid tumors harboring TP53 mutations (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | ovarian carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 4 of the patients achieved PR had ovarian carcinoma (OVC), and TP53 mutations were identified in 2 of the OVC patients with biopsies available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | endometrial carcinoma | predicted - sensitive | Adavosertib | Case Reports/Case Series | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 2 of the patients achieved PR had endometrial carcinoma (EC), and TP53 mutations were identified in 1 of the EC patients with biopsy available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
| TP53 mutant | acute myeloid leukemia | predicted - sensitive | Azacitidine + Magrolimab | Phase I | Actionable | In a Phase Ib trial, Magrolimab (Hu5F9-G4) and Vidaza (azacitidine) combination therapy was well tolerated, and resulted in complete response in 42% (5/12), complete response with incomplete hematologic recovery in 33% (4/12), and stable disease in 17% (2/12) of patients with acute myeloid leukemia harboring TP53 mutations and unfit for chemotherapy (J Clin Oncol 38: 2020 (suppl; abstr 7507); NCT03248479). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | predicted - sensitive | CG-806 | Case Reports/Case Series | Actionable | In a Phase I trial, CG-806 treatment was well-tolerated, and a patient with chronic lymphocytic leukemia harboring a TP53 mutation stayed on treatment for more than 8 cycles (25th Annual Congress of EHA (Jun 2020), Abstract EP711; NCT03893682). | detail... |
| NTRK1 fusion | thyroid cancer | predicted - sensitive | Larotrectinib | Phase II | Actionable | In a combined analysis of two clinical trials, Vitrakvi (larotrectinib) treatment demonstrated a favorable safety profile, resulted in an objective response rate of 75% (21/28, 2 complete responses, 19 partial responses) in patients with non-medullary, advanced thyroid cancer harboring NTRK1 (n=12) or NTRK3 (n=16) fusions, with median progression-free survival (PFS) not reached and a 12-month PFS rate of 81% (Annals of Oncology (2020) 31 (suppl_4): S1086; NCT02122913, NCT02576431). | detail... |
| NTRK1 fusion | lung cancer | predicted - sensitive | Larotrectinib | Phase II | Actionable | In a combined analysis of two clinical trials, Vitrakvi (larotrectinib) treatment demonstrated safety and resulted in an objective response rate (ORR) of 73% (11/15, 1 complete response, 10 partial responses) in 15 evaluable lung cancer patients of 20 harboring NTRK1 (n=16) or NTRK3 (n=4) fusions, with median progression-free survival (PFS) of 35.4 mo, a 12-mo PFS rate of 65%, and 33.9 mo duration of response, and ORR in patients with CNS metastasis was 63% (5/8) (PMID: 35085007; NCT02122913, NCT02576431). | 35085007 |
| TP53 mutant | esophagus adenocarcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal adenocarcinoma cells to radiation therapy, resulting in inhibition of phosphorylation of Wee1 and Cdk1, reduced colony formation, and increased DNA damage and mitotic cell death in culture, and tumor growth inhibition and regression in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus squamous cell carcinoma | sensitive | Adavosertib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment enhanced sensitivity of TP53-mutant esophageal squamous cell carcinoma cells to radiation therapy, resulting in decreased colony formation in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus squamous cell carcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited viability of TP53-mutant esophageal squamous cell carcinoma cells in culture (PMID: 32220892). | 32220892 |
| TP53 mutant | esophagus adenocarcinoma | predicted - sensitive | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment inhibited phosphorylation of Wee1 and Cdk1, and reduced viability of TP53-mutant esophageal adenocarcinoma cells in culture, and led to partial tumor growth delay in cell line xenograft models (PMID: 32220892). | 32220892 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Alemtuzumab + Rituximab | Guideline | Actionable | Campath (alemtuzumab) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Rituximab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Obinutuzumab | Guideline | Actionable | Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Idelalisib | Guideline | Actionable | Zydelig (idelalisib) is included in the guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Lenalidomide + Rituximab | Guideline | Actionable | Revlimid (lenalidomide) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| NTRK1 fusion | gastrointestinal stromal tumor | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org). | detail... |
| NTRK1 fusion | gastrointestinal stromal tumor | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | predicted - sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as first-line therapy (category 2A) and second line therapy or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| NTRK1 fusion | Erdheim-Chester disease | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | Erdheim-Chester disease | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org). | detail... |
| TP53 mutant | high grade glioma | predicted - sensitive | AZ32 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ32 treatment increased sensitivity to radiotherapy in TP53 mutant mouse glioma cells, resulting in reduced cell survival and impaired DNA damage response in culture, and prolonged survival and significantly increased apoptosis of tumor cells compared to normal brain cells (p<0.01) in syngeneic intracranial tumor models (PMID: 29769307). | 29769307 |
| TP53 mutant | high grade glioma | no benefit | AZ31 + Radiotherapy | Preclinical | Actionable | In a preclinical study, AZ31 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, but failed to radiosensitize tumors in syngeneic mouse models due to poor blood-brain barrier permeability (PMID: 29769307). | 29769307 |
| TP53 mutant | high grade glioma | predicted - sensitive | KU-60019 + Radiotherapy | Preclinical | Actionable | In a preclinical study, KU-60019 treatment increased sensitivity to radiotherapy in TP53-mutant mouse glioma cells in culture, and the combination prolonged survival in syngeneic intracranial tumor models compared to radiation alone (PMID: 29769307). | 29769307 |
| NTRK1 fusion | low grade glioma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | low grade glioma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | glioblastoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | glioblastoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic astrocytoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic astrocytoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic oligodendroglioma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic oligodendroglioma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| TP53 mutant | nephroblastoma | not applicable | N/A | Guideline | Risk Factor | Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing Wilms tumor (nephroblastoma) (NCCN.org). | detail... |
| NTRK1 fusion | rectum cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | colon cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | gastrointestinal stromal tumor | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with advanced/metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (PMID: 34560242; ESMO.org). | detail... 34560242 |
| NTRK1 fusion | gastrointestinal stromal tumor | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with advanced/metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (PMID: 34560242; ESMO.org). | detail... 34560242 |
| NTRK1 fusion | small intestine adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | ampulla of Vater adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org). | detail... |
| NTRK1 fusion | ampulla of Vater adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org). | detail... |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Entrectinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival no reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 60% (9/15) in patients harboring fusions in NTRK1/2/3 (PMID: 35395680; NCT02650401). | 35395680 |
| NTRK1 fusion | differentiated high-grade thyroid carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for adult or pediatric patients 12 years or older with metastatic differentiated thyroid gland carcinoma harboring NTRK fusions that have progressed on prior therapies (PMID: 31549998, PMID: 35491008; ESMO.org). | 35491008 31549998 detail... |
| NTRK1 fusion | differentiated high-grade thyroid carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for adult or pediatric patients 12 years or older with metastatic or unresectable differentiated thyroid gland carcinoma harboring NTRK fusions that have progressed on prior therapies (PMID: 31549998, PMID: 35491008; ESMO.org). | detail... 35491008 31549998 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Ibrutinib | Guideline | Actionable | Imbruvica (ibrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Obinutuzumab + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) and Gazyva (obinutuzumab) combination therapy is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | 38969011 detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Venetoclax | Guideline | Actionable | Venclexta (venetoclax) is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Idelalisib + Rituximab | Guideline | Actionable | Zydelig (idelalisib) and Rituxan (rituximab) combination therapy is included in guidelines as first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| NTRK1 rearrange | sarcoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as a standard treatment for patients with advanced sarcomas harboring NTRK rearrangement (PMID: 34303806; ESMO.org). | detail... 34303806 |
| NTRK1 rearrange | sarcoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as a standard treatment for patients with advanced sarcomas harboring NTRK rearrangement (PMID: 34303806; ESMO.org). | detail... 34303806 |
| NTRK1 fusion | glioblastoma | predicted - sensitive | Carboplatin + Etoposide + Larotrectinib | Case Reports/Case Series | Actionable | In a clinical case study, Vitrakvi (larotrectinib), Paraplatin (carboplatin), and Vepesid (etoposide) combination treatment resulted in complete tumor regression after 8 weeks in a pediatric patient with congenital spinal cord glioblastoma harboring an NTRK1 fusion, who remained tumor-free at 17 months (PMID: 34895532). | 34895532 |
| NTRK1 fusion | Advanced Solid Tumor | predicted - sensitive | Zurletrectinib | Case Reports/Case Series | Actionable | In a Phase I trial, Zurletrectinib treatment was well tolerated and resulted in an overall response rate of 66.7% (4/6, all partial responses) and a disease control rate of 100% (6/6) in patients with NTRK fusion-positive advanced solid tumors, including one partial response with a measurable decrease in the brain lesion (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3106; NCT04685226). | detail... |
| NTRK1 fusion | central nervous system cancer | sensitive | Larotrectinib | Phase II | Actionable | In two Phase II trials, Vitrakvi (larotrectinib) treatment resulted in an objective response rate of 30% (10/33, 3 complete responses, 7 partial responses) in pediatric and adult patients with primary central nervous system tumors harboring NTRK fusions including high grade (n=19) and low grade (n=8) gliomas, with a 24-week disease control rate of 73% and a 12-month progression-free survival rate of 56% (PMID: 34850167; NCT02637687, NCT02576431). | 34850167 |
| NTRK1 fusion | high grade glioma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org). | detail... |
| NTRK1 fusion | high grade glioma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org). | detail... |
| NTRK1 fusion | neuroendocrine tumor | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org). | detail... |
| NTRK1 fusion | neuroendocrine tumor | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org). | detail... |
| NTRK1 fusion | mammary analogue secretory carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent or metastatic salivary gland secretory carcinoma harboring NTRK fusions (PMID: 36567082; ESMO.org). | detail... 36567082 |
| NTRK1 fusion | mammary analogue secretory carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with recurrent or metastatic salivary gland secretory carcinoma harboring NTRK fusions (PMID: 36567082; ESMO.org). | detail... 36567082 |
| NTRK1 fusion | biliary tract cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second or later-line therapy for patients with biliary tract cancer harboring an NTRK fusion (PMID: 39864891; ESMO.org). | detail... 39864891 |
| NTRK1 fusion | biliary tract cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second or later-line therapy for patients with biliary tract cancer harboring an NTRK fusion (PMID: 39864891; ESMO.org). | detail... 39864891 |
| NTRK1 fusion | Cancer of Unknown Primary | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with cancer of unknown primary harboring NTRK fusions (PMID: 36563965; ESMO.org). | 36563965 detail... |
| NTRK1 fusion | Cancer of Unknown Primary | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with cancer of unknown primary harboring NTRK fusions (PMID: 36563965; ESMO.org). | 36563965 detail... |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Larotrectinib | Clinical Study - Cohort | Actionable | In a combined analysis of three trials, Vitrakvi (larotrectinib) resulted in improved median overall survival (39.7 vs 10.2 months) and a 78% lower risk of death (HR=0.22, P=0.001) compared to standard of care treatment in patients with advanced solid tumors harboring NTRK fusions (PMID: 36689698; NCT02122913, NCT02637687, and NCT02576431). | 36689698 |
| NTRK1 fusion | esophagus squamous cell carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | esophagus squamous cell carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | colorectal cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic colorectal cancer harboring an NTRK fusion (PMID: 36307056; ESMO.org). | 36307056 detail... |
| NTRK1 fusion | colorectal cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with metastatic colorectal cancer harboring an NTRK fusion (PMID: 36307056; ESMO.org). | 36307056 detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an NTRK fusion with no satisfactory treatment options (PMID: 36872130; ESMO.org). | detail... 36872130 |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an NTRK fusion with no satisfactory treatment options (PMID: 36872130; ESMO.org). | 36872130 detail... |
| TP53 mutant | B-cell acute lymphoblastic leukemia | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Pirtobrutinib | Guideline | Actionable | Jaypirca (pirtobrutinib) is included in guidelines (category 1) as second-line or subsequent therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| NTRK1 fusion | pancreatic cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic pancreatic cancer harboring an NTRK fusion (PMID: 37678671; ESMO.org). | detail... 37678671 |
| NTRK1 fusion | pancreatic cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with metastatic pancreatic cancer harboring an NTRK fusion (PMID: 37678671; ESMO.org). | 37678671 detail... |
| NTRK1 fusion | Adenocarcinoma of Unknown Primary | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | Adenocarcinoma of Unknown Primary | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | Squamous Cell Carcinoma of Unknown Primary | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | Squamous Cell Carcinoma of Unknown Primary | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Obinutuzumab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor and BLC2 inhibitor-based regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is included in guidelines as first-line (category 2A) and second-line or subsequent therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | not applicable | N/A | Guideline | Prognostic | TP53 mutations are associated with poor prognosis in patients with mantle cell lymphoma who are treated with conventional therapy, including transplant (NCCN.org). | detail... |
| NTRK1 fusion | vaginal carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vaginal carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing breast cancer (NCCN.org). | detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Repotrectinib | Phase Ib/II | Actionable | In a Phase I/II (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate (cORR) of 62%, a 12-mo duration of response (DOR) of 92%, and 12-mo progression-free survival (PFS) of 64% in TKI-naive (n=21) patients with non-small cell lung cancer harboring NTRK fusions, and a 42% cORR, 44% 12-mo DOR, and 23% 12-mo PFS in TKI-pretreated (n=14) patients (Ann Oncol (2023) 34 (suppl_2): S787-S788; NCT03093116). | detail... |
| NTRK1 fusion | extrahepatic bile duct carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| NTRK1 fusion | intrahepatic cholangiocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| NTRK1 fusion | gallbladder cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including gallbladder cancer (NCCN.org). | detail... |
| NTRK1 fusion | breast cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | colon cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic colon cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | rectum cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | small intestine adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | ovary epithelial cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | hepatocellular carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | ampulla of Vater adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org). | detail... |
| NTRK1 fusion | gastrointestinal stromal tumor | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as neoadjuvant therapy (category 2B) for patients with resectable disease and as first-line or second-line systemic therapy (category 2A) for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org). | detail... |
| NTRK1 fusion | Erdheim-Chester disease | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | soft tissue sarcoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as a preferred first-line or subsequent therapy for patients with soft tissue sarcoma harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | Squamous Cell Carcinoma of Unknown Primary | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | Adenocarcinoma of Unknown Primary | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org). | detail... |
| NTRK1 fusion | pancreatic adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), or with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good (category 2A), intermediate, or poor (category 2B) PS (NCCN.org). | detail... |
| NTRK1 fusion | esophagus adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | esophagus squamous cell carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | gastroesophageal junction adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | neuroendocrine tumor | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on a prior NTRK-targeted therapy (NCCN.org). | detail... |
| NTRK1 fusion | glioblastoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | pilocytic astrocytoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | pleomorphic xanthoastrocytoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | subependymal giant cell astrocytoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | papillary thyroid carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | follicular thyroid carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | oncocytic carcinoma of the thyroid | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org). | detail... |
| NTRK1 fusion | anaplastic thyroid carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia | sensitive | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is included in guidelines as preferred first-line therapy for patients with advanced chronic lymphocytic leukemia harboring TP53 mutations and for patients with relapsed or refractory disease (PMID: 38969011; ESMO.org). | detail... 38969011 |
| NTRK1 fusion | biliary tract cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) for biliary tract cancer patients harboring NTRK fusions who have progressed on or are intolerant of prior therapies (PMID: 39232586; ESMO.org). | 39232586 detail... |
| NTRK1 fusion | biliary tract cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) for biliary tract cancer patients harboring NTRK fusions who have progressed on or are intolerant of prior therapies (PMID: 39232586; ESMO.org). | 39232586 detail... |
| NTRK1 fusion | stomach cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | salivary gland cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring an NTRK1 fusion (NCCN.org). | detail... |
| NTRK1 fusion | vaginal carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion who are naive to prior NTRK targeted therapy or have progressed on prior NTRK therapy (NCCN.org). | detail... |
| NTRK1 fusion | spindle cell sarcoma | predicted - sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a Phase II trial (ADVL1823), first-line Vitrakvi (larotrectinib) treatment resulted in an objective response rate of 60% (9/15), 2-year event-free survival of 80%, and 2-year overall survival rate of 93.3% in patients with NTRK-rearranged solid tumors, including 5 partial responses in 7 patients with spindle cell neoplasm harboring NTRK1 fusion (n=4) or NTRK3 fusion (n=3) (PMID: 39652801; NCT03834961). | 39652801 |
| NTRK1 fusion | cervical cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva squamous cell carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva squamous cell carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva squamous cell carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | vulva adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | sensitive | Obinutuzumab + Venetoclax + Zanubrutinib | Guideline | Actionable | The combination of Brukinsa (zanubrutinib), Gazyva (obinutuzumab), and Venclexta (venetoclax) is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | sensitive | Acalabrutinib + Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Prednisone + Rituximab + Vincristine Sulfate | Guideline | Actionable | The combination of Calquence (acalabrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | sensitive | Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Ibrutinib + Prednisone + Rituximab + Vincristine Sulfate | Guideline | Actionable | The combination of Imbruvica (ibrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | mantle cell lymphoma | sensitive | Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Prednisone + Rituximab + Vincristine Sulfate + Zanubrutinib | Guideline | Actionable | The combination of Brukinsa (zanubrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org). | detail... |
| NTRK1 fusion | high grade glioma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org). | detail... |
| NTRK1 fusion | endometrial carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent-line therapy for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | uterine corpus sarcoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Acalabrutinib + Obinutuzumab + Venetoclax | Guideline | Actionable | The combination of Venclexta (venetoclax), Gazyva (obinutuzumab), and Calquence (acalabrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Lisocabtagene maraleucel | Guideline | Actionable | Breyanzi (lisocabtagene maraleucel) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| NTRK1 fusion | biliary tract cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as second or later-line therapy for patients with biliary tract cancer harboring an NTRK fusion (PMID: 39864891; ESMO.org). | 39864891 detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) for advanced and metastatic non-small cell lung cancer patients harboring NTRK fusions who have no other treatment options (PMID: 39615406; ESMO.org). | 39615406 detail... |
| NTRK1 fusion | lung non-small cell carcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) for advanced and metastatic non-small cell lung cancer patients harboring NTRK fusions who have no other treatment options (PMID: 39615406; ESMO.org). | 39615406 detail... |
| NTRK1 fusion | congenital fibrosarcoma | sensitive | Larotrectinib | Clinical Study - Cohort | Actionable | In a retrospective study (EPI VITRAKVI), Vitrakvi (Larotrectinib) treatment in patients with infantile fibrosarcoma harboring an NTRK fusion resulted in an objective response rate of 90.2%, disease control rate of 100%, and an 80% decreased likelihood of a medical treatment failure event (7.8% vs 35.7%, HR=0.20, P=0.0060) compared to chemotherapy-based treatment (PMID: 38657345; NCT05236257). | 38657345 |
| NTRK1 fusion | Advanced Solid Tumor | sensitive | Entrectinib | Clinical Study - Cohort | Actionable | In a combined analysis of 3 clinical trials (STARTRK-NG, TAPISTRY, STARTRK-2), Rozlytrek (entrectinib) treatment resulted in an objective response rate (ORR) of 72.7% (32/44, 20 complete (CR) and 12 partial (PR) responses) in pediatric patients (median age 4.0 yo) with solid tumors harboring NTRK fusions, with median time to response of 1.86 mo, ORR was 91.7% (22/24, 15 CR, 7 PR) in patients with extracranial solid tumors (PMID: 40086048; NCT02650401, NCT04589845, NCT02568267). | 40086048 |
| NTRK1 fusion | central nervous system cancer | sensitive | Entrectinib | Clinical Study - Cohort | Actionable | In a combined analysis of 3 clinical trials (STARTRK-NG, TAPISTRY, STARTRK-2), Rozlytrek (entrectinib) treatment resulted in an objective response rate (ORR) of 72.7% (32/44, 20 complete (CR) and 12 partial (PR) responses) in pediatric patients (median age 4.0 yo) with solid tumors harboring NTRK fusions, with median time to response of 1.86 mo, ORR was 50.0% (10/20, 5 CR, 5 PR) in patients with CNS tumors (PMID: 40086048; NCT02650401, NCT04589845, NCT02568267). | 40086048 |
| NTRK1 fusion | high grade glioma | sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a clinical study, Vitrakvi (larotrectinib) treatment resulted in an overall response rate of 100% (8/8, 4 complete responses, 3 partial responses, 1 minor response) in patients with pediatric high-grade glioma harboring NTRK fusions (PMID: 39625867). | 39625867 |
| NTRK1 fusion | gastrointestinal system cancer | predicted - sensitive | Larotrectinib | Phase II | Actionable | In a Phase II trial (NAVIGATE), Vitrakvi (larotrectinib) treatment resulted in an overall response rate (ORR) of 28% (12/43, 3 complete and 9 partial responses) and stable disease in 44% (19/43) of gastrointestinal cancer patients harboring NTRK fusions, with a median duration of response of 27 mo, median progression-free survival of 6 mo, and median overall survival of 13 mo; ORR was 38% (10/26) in patients with NTRK1 fusions (PMID: 40068370; NCT02576431). | 40068370 |
| NTRK1 fusion | colorectal cancer | sensitive | Larotrectinib | Phase II | Actionable | In a Phase II trial (NAVIGATE), Vitrakvi (larotrectinib) treatment resulted in an overall response rate (ORR) of 28% (12/43, 3 complete and 9 partial responses) and stable disease in 44% (19/43) of gastrointestinal cancer patients harboring NTRK fusions, ORR was 44% (11/25) in colorectal cancer patients and 40% (6/15) in those with microsatellite instability-high colorectal cancer (PMID: 40068370; NCT02576431). | 40068370 |
| TP53 mutant | adrenocortical carcinoma | not applicable | N/A | Guideline | Risk Factor | Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing adrenocortical carcinoma (NCCN.org). | detail... |
| NTRK1 fusion | pancreatic cancer | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as third-line therapy for patients with pancreatic cancer harboring an NTRK fusion (PMID: 41067164; ESMO.org). | detail... 41067164 |
| NTRK1 fusion | pancreatic cancer | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as third-line therapy for patients with pancreatic cancer harboring an NTRK fusion (PMID: 41067164; ESMO.org). | detail... 41067164 |
| NTRK1 fusion | pancreatic cancer | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as third-line therapy for patients with pancreatic cancer harboring an NTRK fusion (PMID: 41067164; ESMO.org). | detail... 41067164 |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Lisocabtagene maraleucel | Guideline | Actionable | Breyanzi (lisocabtagene maraleucel) in combination with Imbruvica (ibrutinib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org). | detail... |
| TP53 mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Venetoclax + Zanubrutinib | Guideline | Actionable | Venclexta (venetoclax) combined with Brukinsa (zanubrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). | detail... |
| NTRK1 fusion | appendix adenocarcinoma | sensitive | Larotrectinib | Guideline | Actionable | Vitrakvi (larotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | appendix adenocarcinoma | sensitive | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 fusion | appendix adenocarcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org). | detail... |
| NTRK1 rearrange | colon adenocarcinoma | predicted - sensitive | Larotrectinib | Case Reports/Case Series | Actionable | In a clinical case study, adjuvant Vitrakvi (Larotrectinib) treatment resulted in decrease in the metastases and RECIST stabilization with a progression-free survival of 21 months in a patient with metastatic colon adenocarcinoma harboring an NTRK1 rearrangement who had comorbidities contraindicating the use of chemotherapy (PMID: 41571604). | 41571604 |
| TP53 mutant | mantle cell lymphoma | sensitive | Acalabrutinib + Rituximab | Guideline | Actionable | The combination of Calquence (acalabrutinib) and Rituxan (rituximab) is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org). | detail... |
| TP53 mutant | skin melanoma | not applicable | N/A | Guideline | Risk Factor | Germline TP53 mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org). | detail... |