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Therapy Name | Talazoparib |
Synonyms | |
Therapy Description |
Talzenna (talazoparib) is an inhibitor of PARP1 and PARP2, which prevents the DNA repair of single strand DNA breaks, thus causing the accumulation of DNA strand breaks, genomic instability and apoptosis, and leads to lethality in homologous recombination repair deficient cells (PMID: 28242752). Talzenna (talazoparib) is FDA approved for use in patients with ERBB2 (HER2)-negative breast cancer harboring deleterious or suspected deleterious germline BRCA mutations, and in combination with Xtandi (enzalutamide) in patients with homologous recombination repair gene (ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C)-mutated metastatic castration-resistant prostate cancer (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Talazoparib | Talzenna | BMN673 | PARP Inhibitor (Pan) 31 | Talzenna (talazoparib) is an inhibitor of PARP1 and PARP2, which prevents the DNA repair of single strand DNA breaks, thus causing the accumulation of DNA strand breaks, genomic instability and apoptosis, and leads to lethality in homologous recombination repair deficient cells (PMID: 28242752). Talzenna (talazoparib) is FDA approved for use in patients with ERBB2 (HER2)-negative breast cancer harboring deleterious or suspected deleterious germline BRCA mutations, and in combination with Xtandi (enzalutamide) in patients with homologous recombination repair gene (ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C)-mutated metastatic castration-resistant prostate cancer (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RAD51C H192_R193delinsGG | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C H192_R193delinsGG demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
RAD51C R193W | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C R193W demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
RAD51D S207L | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing RAD51D S207L demonstrated decreased survival when treated with Talzenna (talazoparib) in culture (PMID: 28646019). | 28646019 |
RAD51C R193L | ovarian carcinoma | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, ovarian carcinoma cells expressing RAD51C R193L demonstrated resistance to Talzenna (talazoparib) in culture (PMID: 28588062). | 28588062 |
IDH1 R132H | colorectal cancer | predicted - sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring IDH1 R132H were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
TET2 loss | acute myeloid leukemia | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring TET2 loss along with a FLT3-ITD mutation in culture (PMID: 34215619). | 34215619 |
ATM S1599* | appendix cancer | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment resulted in a clinical benefit rate (CBR) of 22.8% (18/79, 1 complete and 7 partial responses, 10 with stable disease >/=24 weeks) in patients with advanced solid tumors harboring mutations in DNA damage repair genes, including a partial response lasting 12 weeks in an appendiceal cancer patient harboring ATM S1599* (PMID: 39085400; NCT02286687). | 39085400 |
ATM G1676fs | cholangiocarcinoma | predicted - sensitive | Talazoparib | Case Reports/Case Series | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment resulted in a clinical benefit rate (CBR) of 22.8% (18/79, 1 complete and 7 partial responses, 10 with stable disease >/=24 weeks) in patients with advanced solid tumors harboring mutations in DNA damage repair genes, including a partial response lasting 16 weeks in a cholangiocarcinoma cancer patient harboring ATM G1676fs (PMID: 39085400; NCT02286687). | 39085400 |
DNMT3A loss TET2 loss | acute myeloid leukemia | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) decreased colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along with a FLT3-ITD mutation in culture (PMID: 34215619). | 34215619 |
IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
PTEN loss | Advanced Solid Tumor | no benefit | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687). | 39085400 |
IDH1 R132C | high grade glioma | sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
BRAF V600E NRAS Q61R | melanoma | sensitive | Talazoparib | Preclinical - Pdx | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61R (PMID: 37729428). | 37729428 |
IDH1 R132H | high grade glioma | sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived glioma cells harboring IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
IDH1 R132H | high grade glioma | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H in culture (PMID: 34118569). | 34118569 |
IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
DNMT3A loss | acute myeloid leukemia | resistant | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, mouse acute myeloid leukmia cells harboring DNMT3A loss along with a FLT3-ITD mutation were resistant to Talzenna (talazoparib) in culture (PMID: 34215619). | 34215619 |
PTEN Y336* | breast cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells expressing PTEN Y336* demonstrated increased sensitivity to Talzenna (talazoparib) compared to cells expressing wild-type Pten in culture (PMID: 25946202}. | 25946202 |
PTEN negative | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, PTEN-deficient cancer cell lines with DNA repair deficiency demonstrated high sensitivity to the PARP inhibitor Talzenna (talazoparib) (PMID: 23881923). | 23881923 |
IDH1 R132H | colon carcinoma | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
IDH1 R132H | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
ATM dec exp | breast cancer | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, knockdown of ATM expression sensitized breast cancer cells to treatment with Talzenna (talazoparib) in culture (PMID: 23881923). | 23881923 |
BRAF V600E NRAS Q61K | melanoma | sensitive | Talazoparib | Preclinical - Pdx | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited tumor growth and led to improved survival compared to controls in a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and NRAS Q61K (PMID: 37729428). | 37729428 |
PTEN inact mut | Advanced Solid Tumor | no benefit | Talazoparib | Phase II | Actionable | In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687). | 39085400 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02997176 | Phase I | Talazoparib | An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800) | Completed | USA | 0 |
NCT02316834 | Phase I | Talazoparib | POSITION: A PilOt Study of InducTion PARP InhibitiON in Ovarian Cancer | Completed | USA | 0 |
NCT03042910 | Phase I | Talazoparib | A Study to Assess the Effects of Talazoparib on Cardiac Repolarization in Patients With Advanced Solid Tumors | Completed | USA | 0 |
NCT05898399 | Phase Ib/II | Olaparib ART6043 Talazoparib ART6043 + Olaparib ART6043 + Talazoparib | Study of ART6043 in Advanced/Metastatic Solid Tumors Patients | Recruiting | USA | 0 |
NCT03377556 | Phase II | Talazoparib | Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer | Completed | USA | CAN | 0 |
NCT02326844 | Phase II | Talazoparib | BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment | Terminated | USA | 0 |
NCT02925234 | Phase II | Crizotinib Sunitinib Niraparib Olaparib Lorlatinib Erdafitinib Talazoparib Dacomitinib Axitinib Panitumumab | The Drug Rediscovery Protocol (DRUP Trial) (DRUP) | Recruiting | NLD | 0 |
NCT03964532 | Phase Ib/II | Talazoparib Avelumab + Talazoparib | TALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer | Active, not recruiting | USA | 0 |
NCT04801966 | Phase 0 | Palbociclib Alpelisib Atezolizumab Vemurafenib Ribociclib Talazoparib Cobimetinib Trametinib Abemaciclib Dabrafenib Nivolumab Binimetinib Pembrolizumab Encorafenib | Safety and Oversight of the Individually Tailored Treatment Approach: A Novel Pilot Study (TAILOR) | Terminated | AUS | 0 |
NCT06193525 | Phase II | Talazoparib | FUnctional Selection of Advanced Breast Cancer Patients for Talazoparib Treatment Using the REpair Capacity (RECAP) Test (FUTURE) | Recruiting | NLD | 0 |
NCT03990896 | Phase II | Talazoparib | Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial | Recruiting | USA | 0 |
NCT01286987 | Phase I | Talazoparib | Study of BMN 673, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors | Completed | USA | GBR | 0 |
NCT03974217 | Phase I | Talazoparib | Talazoparib for Cohesin-Mutated AML and MDS With Excess Blasts | Recruiting | USA | 0 |
NCT02567396 | Phase I | Talazoparib | Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction | Withdrawn | 0 | |
NCT05725200 | Phase II | Dasatinib Palbociclib Gemcitabine Trastuzumab Cetuximab Pertuzumab Panobinostat Alectinib Venetoclax Larotrectinib Encorafenib Everolimus Idelalisib Crizotinib Pembrolizumab Methotrexate Talazoparib | Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer (EVIDENT) | Recruiting | NOR | 0 |
NCT02693535 | Phase II | Cobimetinib + Vemurafenib Atezolizumab + Talazoparib Regorafenib Larotrectinib Trastuzumab + Tucatinib Ipilimumab + Nivolumab Palbociclib Afatinib Entrectinib Talazoparib Pembrolizumab Temsirolimus Pertuzumab + Trastuzumab Atezolizumab + Pertuzumab/trastuzumab/hyaluronidase-zzxf Crizotinib Abemaciclib Sunitinib Olaparib | TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (TAPUR) | Recruiting | USA | 0 |
NCT04756765 | Phase II | Talazoparib | Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer | Recruiting | USA | 0 |
NCT02921919 | Phase II | Talazoparib | Open-Label Extension and Safety Study of Talazoparib | Completed | USA | POL | HUN | GBR | FRA | DEU | CAN | 2 |
NCT02034916 | Phase II | Talazoparib | A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study) | Terminated | USA | GBR | FRA | ESP | DEU | 0 |
NCT04462809 | Phase II | Talazoparib | Efficacy of a Maintenance Treatment With TALAzoparib Following First Line Platinum-based Chemotherapy in Malignant MESOthelioma (TALAMESO) | Unknown status | 0 | |
NCT04170946 | Phase I | Talazoparib | Talazoparib and Thoracic RT for ES-SCLC | Recruiting | CAN | 0 |
NCT03148795 | Phase II | Talazoparib | A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer | Completed | USA | POL | NLD | ITA | HUN | GBR | FRA | ESP | DEU | BRA | BEL | AUT | AUS | 1 |
NCT05097599 | Phase II | Binimetinib + Encorafenib Trastuzumab deruxtecan Enfortumab vedotin-ejfv Talazoparib Lorlatinib | Strata PATH (Precision Indications for Approved Therapies) (Strata PATH) | Active, not recruiting | USA | 0 |
NCT02537561 | Phase I | Talazoparib Cisplatin + Gemcitabine | Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors | Withdrawn | 0 | |
NCT02401347 | Phase II | Talazoparib | Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors | Completed | USA | 0 |
NCT03395197 | Phase III | Talazoparib | Talazoparib + NHT vs. NHT Monotherapy in DDR+ mCRPC (TALAPRO-2) | Active, not recruiting | USA | SWE | POL | NZL | NOR | ITA | ISR | HUN | GBR | FRA | FIN | ESP | DEU | CZE | CAN | BRA | BEL | AUS | ARG | 7 |
NCT02286687 | Phase II | Talazoparib | Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes | Active, not recruiting | USA | 0 |
NCT04550494 | Phase II | Talazoparib | Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations | Recruiting | USA | 0 |
NCT01945775 | Phase III | Gemcitabine Capecitabine Vinorelbine Talazoparib Eribulin | A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study) (EMBRACA) | Completed | USA | POL | ITA | ISR | IRL | GBR | FRA | ESP | DEU | BRA | BEL | AUS | 4 |
NCT02154490 | Phase II | Docetaxel Nivolumab Palbociclib Durvalumab Ipilimumab + Nivolumab Fexagratinib Taselisib Durvalumab + Tremelimumab Erlotinib + Rilotumumab Talazoparib Erlotinib | Lung-MAP: Biomarker-Targeted Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer | Completed | USA | CAN | 0 |
NCT04672460 | Phase I | Talazoparib | A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors | Completed | USA | AUS | 0 |
NCT04598321 | Phase I | Talazoparib | BrUOG 390: Neoadjuvant Treatment With Talazoparib | Terminated | USA | 0 |
NCT02997163 | Phase I | Talazoparib | An Open-Label Pharmacokinetics and Safety Study of Talazoparib | Completed | USA | CAN | 0 |
NCT03968406 | Phase I | Talazoparib | Talazoparib and Radiation Therapy in Treating Patients With Locally Recurrent Gynecologic Cancers | Recruiting | USA | 0 |
NCT03499353 | Phase II | Talazoparib | Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer | Terminated | USA | 0 |
NCT02282345 | Phase II | Talazoparib | Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer | Completed | USA | 0 |
NCT01989546 | Phase Ib/II | Talazoparib | Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations | Completed | USA | 0 |