|
ATM inact mut
|
lymphoid leukemia
|
sensitive
|
Olaparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, lymphoblastoid cell lines with ATM inactivation derived from ataxia-telangiectasia patients demonstrated increased sensitivity to Lynparza (olaparib) in culture, compared to ATM wild-type cell lines (PMID: 20739657).
|
20739657
|
|
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
|
|
ATM mutant
|
prostate cancer
|
sensitive
|
Olaparib
|
Phase II |
Actionable |
In a Phase II clinical trial, 80% (4/5) of metastatic castration-resistant prostate cancer patients with ATM truncation mutations demonstrated response to Lynparza (olaparib) treatment (Cancer Res August 1, 2015 75:CT322).
|
detail...
|
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
Phase II |
Actionable |
In a Phase II trial (TOPARP-B), Lynparza (olaparib) treatment resulted in a composite overall response rate of 36.8% (7/19) and a RECIST objective response rate of 8.3% (1/12) in patients with castration-resistant prostate cancer harboring deleterious ATM mutations (PMID: 31806540; NCT01682772).
|
31806540
|
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious BRCA or ATM mutations, HR for progression or death was 1.04 in ATM-mutant patients (PMID: 32343890; NCT02987543).
|
detail...
32343890
detail...
|
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Olaparib
|
Guideline |
Actionable |
Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in ATM (NCCN.org).
|
detail...
|
|
ATM loss
|
lung non-small cell carcinoma
|
sensitive
|
Ceralasertib + Cisplatin
|
Preclinical |
Actionable |
In a preclinical study, AZD6738 and Platinol (cisplatin) synergistically induced cell death in ATM-deficient non-small cell lung carcinoma cell lines in culture, and caused rapid tumor regression in xenograft models (PMID: 26517239).
|
26517239
|
|
ATM loss
|
chronic lymphocytic leukemia
|
sensitive
|
AZD6482
|
Preclinical |
Actionable |
In a preclinical study, AZD6482 induced cell death in ATM-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132).
|
26563132
|
|
ATM loss
|
chronic lymphocytic leukemia
|
sensitive
|
Ceralasertib + Ibrutinib
|
Preclinical |
Actionable |
In a preclinical study, AZD6738 sensitized ATM-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132).
|
26563132
|
|
ATM loss
|
Advanced Solid Tumor
|
sensitive
|
YU238259
|
Preclinical |
Actionable |
In a preclinical study, YU238259 demonstrated increased cytotoxicity in ATM-deficient transformed human cell lines in culture (PMID: 26116172).
|
26116172
|
|
ATM inact mut
|
Advanced Solid Tumor
|
sensitive
|
E7449
|
Preclinical |
Actionable |
In a preclinical study, E7449 inhibited proliferation of a ATM-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair pathway mutations (PMID: 26513298).
|
26513298
|
|
ATM loss
|
colorectal cancer
|
sensitive
|
Berzosertib
|
Phase I |
Actionable |
In a Phase I trial, Berzosertib (VX-970) treatment resulted in complete response for more than 19 months in a colorectal cancer patient harboring ATM loss (J Clin Oncol 34, 2016 (suppl; abstr 2504)).
|
detail...
|
|
ATM inact mut
|
mantle cell lymphoma
|
sensitive
|
Olaparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, a mantle cell lymphoma cell line with ATM inactivation demonstrated sensitivity to Lynparza (olaparib) in culture and in xenograft models (PMID: 20739657).
|
20739657
|
|
ATM inact mut
|
chronic lymphocytic leukemia
|
sensitive
|
Olaparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, patient-derived chronic lymphocytic leukemia cells with inactivating mutations in ATM, that had been induced to proliferate in culture, demonstrated increased sensitivity to growth inhibition by Lynparza (olaparib) compared to ATM wild-type cells (PMID: 20739657).
|
20739657
|
|
ATM inact mut
|
mantle cell lymphoma
|
sensitive
|
Bendamustine + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Treanda (bendamustine) in cell culture, resulting in growth inhibition (PMID: 20739657).
|
20739657
|
|
ATM inact mut
|
mantle cell lymphoma
|
sensitive
|
Olaparib + Valproic acid
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Lynparza (olaparib) and valproic acid worked synergistically to inhibit growth of a mantle cell lymphoma cell line harboring an ATM inactivating mutation in culture (PMID: 20739657).
|
20739657
|
|
ATM inact mut
|
mantle cell lymphoma
|
sensitive
|
Fludarabine + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) sensitized a mantle cell lymphoma cell line harboring an ATM inactivating mutation to Fludara (fludarabine) in cell culture, resulting in decreased cell survival (PMID: 20739657).
|
20739657
|
|
ATM dec exp
|
stomach cancer
|
sensitive
|
Veliparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, knockdown of ATM in a gastric cancer cell line resulted in increased sensitivity to Veliparib (ABT-888) in culture and in xenograft models (PMID: 27638859).
|
27638859
|
|
ATM inact mut
|
Advanced Solid Tumor
|
sensitive
|
Veliparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, an ATM-deficient cell line demonstrated increased sensitivity to Veliparib (ABT-888) compared to an ATM-reconstituted cell line, in culture (PMID: 21300883).
|
21300883
|
|
ATM dec exp
|
stomach cancer
|
predicted - sensitive
|
Olaparib + Paclitaxel
|
Phase II |
Actionable |
In a Phase II trial, addition of Lynparza (olaparib) to Taxol (paclitaxel) did not significantly improve progression free survival (5.29 vs 3.68 months) compared to Taxol alone, but did significantly prolong overall survival (HR = 0.35) in metastatic gastric cancer patients with decreased Atm expression (PMID: 26282658; NCT01063517).
|
26282658
|
|
ATM over exp
|
stomach cancer
|
decreased response
|
Veliparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, high ATM expression was associated with decreased response to Veliparib (ABT-888) in gastric cancer cell lines in culture (PMID: 27638859).
|
27638859
|
|
ATM over exp
|
stomach cancer
|
sensitive
|
Irinotecan + Veliparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, the combination of Camptosar (irinotecan) and Veliparib (ABT-888) demonstrated synergy in gastric cancer cell lines with high ATM expression, resulting in increased apoptosis in culture, and enhanced tumor growth inhibition in cell line xenograft models (PMID: 27638859).
|
27638859
|
|
ATM over exp
|
stomach cancer
|
decreased response
|
Irinotecan
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, high ATM expression was associated with decreased response to Camptosaur (irinotecan) in gastric cancer cell lines in culture (PMID: 27638859).
|
27638859
|
|
ATM L804fs ATM S978fs RET M918T
|
medullary thyroid carcinoma
|
predicted - sensitive
|
Everolimus + Vandetanib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, addition of Afinitor (everolimus) to Caprelsa (vandetanib) treatment resulted in significant tumor reduction in a medullary thyroid carcinoma patient harboring ATM L804fs*4, ATM S978fs*12, and RET M918T, that achieved prolonged stable disease on Caprelsa (vandetanib) treatment alone (PMID: 27683183).
|
27683183
|
|
ATM del ATR dec exp
|
Advanced Solid Tumor
|
decreased response
|
PJ34
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, ATM-null transformed cells with decreased Atr expression demonstrated decreased sensitivity to PJ34 in culture (PMID: 21840268).
|
21840268
|
|
ATM mut NRAS Q61R
|
melanoma
|
predicted - sensitive
|
Binimetinib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312).
|
28514312
|
|
ATM loss
|
head and neck cancer
|
predicted - sensitive
|
Ceralasertib + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of AZD6738 and Lynparza (olaparib) resulted in a synergistic effect, demonstrating cell death in head and neck cancer cells harboring ATM loss in culture (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C60).
|
detail...
|
|
ATM negative
|
stomach cancer
|
no benefit
|
Olaparib + Paclitaxel
|
Phase III |
Actionable |
In a Phase III trial (GOLD), addition of Lynparza (olaparib) to Taxol (paclitaxel) did not significantly improve overall survival (12.0 vs 10.0 months, HR=0.73, p=0.25) compared to Taxol (paclitaxel) alone in Asian patients with ATM-negative gastric cancer (PMID: 29103871; NCT01924533).
|
29103871
|
|
ATM positive
|
glioblastoma
|
sensitive
|
AZD1390
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, AZD1390 inhibited Atm activity, sensitized glioblastoma cell lines to radiotherapy in culture, and demonstrated efficacy in mouse models of glioblastoma (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104).
|
detail...
|
|
ATM positive
|
lung cancer
|
sensitive
|
AZD1390
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, AZD1390 inhibited Atm activity, sensitized lung cancer cells to radiotherapy in culture, and demonstrated efficacy in cell line xenograft models (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104).
|
detail...
|
|
ATM T1200Lfs*7 NRAS Q61K TP53 R213*
|
sarcoma
|
predicted - resistant
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, Lynparza (olaparib) treatment resulted in rapid disease progression in a patient with high-grade sarcoma harboring ATM T1200Lfs*7, NRAS Q61K, and TP53 R213* (PMID: 29304353).
|
29304353
|
|
ATM L1449*
|
prostate adenocarcinoma
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, Lynparza (olaparib) treatment resulted in stable disease for more than 6 months in a patient with prostate adenocarcinoma harboring ATM L1449*, amplification of AR, MYC, BCL9, MCL1, MDM4, RPS6KB1, APEX1, PNP, ATP11B, and DCUN1D1, and a TMPRSS2-ERG fusion (PMID: 29304353).
|
29304353
|
|
ATM mutant
|
mantle cell lymphoma
|
predicted - sensitive
|
Ibrutinib + Venetoclax
|
Phase II |
Actionable |
In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391).
|
30455436
|
|
ATM negative
|
Advanced Solid Tumor
|
predicted - sensitive
|
Elimusertib
|
Phase I |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment was tolerated and resulted in an objective response rate of 36.4% (4/11, all partial responses) and a disease control rate of 63.6% (7/11) in patients with advanced solid tumors harboring ATM inactivating mutations and/or ATM protein expression loss (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM inact mut
|
Advanced Solid Tumor
|
predicted - sensitive
|
Elimusertib
|
Phase I |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment was tolerated and resulted in an objective response rate of 36.4% (4/11, all partial responses) and a disease control rate of 63.6% (7/11) in patients with advanced solid tumors harboring ATM inactivating mutations and/or ATM protein expression loss (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM P960H
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm P960H, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM S1455R
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm S1455R, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM V1841I
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm V1841I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM L1874F
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm L1874F, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM H2038Y
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm H2038Y, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM K2749I
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm K2749I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM A59S
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm A59S, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM P604S
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm P604S, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM V519I
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm V519I, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM S824F
|
neuroblastoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm S824F, resulted in decreased cell viability as compared to cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM L1956H
|
neuroblastoma
|
no benefit
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of neuroblastoma cells in culture, transfected with Atm L1956H, resulted in similar cell viability levels as cells carrying wild-type Atm (PMID: 29059438).
|
29059438
|
|
ATM R2691C
|
neuroblastoma
|
no benefit
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment of transformed neuroblastoma cells expressing ATM R2691C resulted in similar cell viability levels to wild-type Atm in culture (PMID: 29059438).
|
29059438
|
|
ATM mutant
|
prostate cancer
|
not applicable
|
N/A
|
Guideline |
Risk Factor |
Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org).
|
detail...
|
|
ATM D2725G
|
lung small cell carcinoma
|
predicted - sensitive
|
Temozolomide + Veliparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted in partial response in a patient with small cell lung cancer harboring ATM D2725G, with a progression-free survival of 9 months and an overall survival of 16 months (PMID: 29906251; NCT01638546).
|
29906251
|
|
ATM S333F
|
lung small cell carcinoma
|
predicted - sensitive
|
Temozolomide + Veliparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted stable disease in a patient with small cell lung cancer harboring ATM S333F, with a progression-free survival of 4.2 months and an overall survival of 4.2 months (PMID: 29906251; NCT01638546).
|
29906251
|
|
ATM V410A
|
lung small cell carcinoma
|
predicted - sensitive
|
Temozolomide + Veliparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, Temodar (temozolomide) and Veliparib (ABT-888) combination treatment resulted stable disease in a patient with small cell lung cancer harboring ATM V410A, with a progression-free survival of 6.3 months and an overall survival of 6.3 months (PMID: 29906251; NCT01638546).
|
29906251
|
|
ATM del
|
head and neck cancer
|
sensitive
|
AZD7648 + Olaparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), resulting in inhibition of Dna-pk phosphorylation, reduced cell viability, genomic instability, cell cycle arrest, and apoptosis in a head and neck cancer cell line with ATM deletion in culture, and inhibition of tumor growth and complete tumor regression in a cell line xenograft model (PMID: 31699977).
|
31699977
|
|
ATM del
|
head and neck cancer
|
sensitive
|
AZD7648
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AZD7648 treatment induced genomic instability, cell cycle arrest, and inhibited viability of an ATM knockout head and neck cancer cell line in culture (PMID: 31699977).
|
31699977
|
|
ATM del
|
head and neck cancer
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment induced genomic instability, cell cycle arrest, and inhibited viability of an ATM knockout head and neck cancer cell line in culture (PMID: 31699977).
|
31699977
|
|
ATM del
|
lung non-small cell carcinoma
|
sensitive
|
AZD7648 + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), inducing cell cycle arrest and inhibiting viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977).
|
31699977
|
|
ATM del
|
lung non-small cell carcinoma
|
sensitive
|
AZD7648
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AZD7648 treatment inhibited viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977).
|
31699977
|
|
ATM del
|
lung non-small cell carcinoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment inhibited viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977).
|
31699977
|
|
ATM inact mut
|
prostate cancer
|
no benefit
|
Rucaparib
|
Phase II |
Actionable |
In a Phase II trial (TRITON2), activity of Rubraca (rucaparib) was limited in the cohort of patients with metastatic castrate-resistant prostate cancer harboring an ATM mutation presumed to be inactivating, with a radiographic response rate of 10.5% (2/19, including 1 patient with co-occurring CHEK2 alteration) and PSA response rate of 4.1% (2/49), and no radiographic responses in 11 patients with biallelic alterations in ATM or 11 patients with germline ATM alterations (PMID: 32086346; NCT02952534).
|
32086346
|
|
ATM inact mut
|
prostate cancer
|
no benefit
|
Rucaparib
|
Phase III |
Actionable |
In a Phase III trial (TRITON3), Rubraca (rucaparib) treatment demonstrated limited efficacy compared to control treatment with Taxotere (docetaxel) in patients with metastatic castration-resistant prostate cancer harboring deleterious ATM mutations, with a median imaging-based progression-free survival of 8.1 months vs. 6.8 months (HR=0.95), a median overall survival of 21.1 months vs. 21.7 months of patients (PMID: 36795891; NCT02975934).
|
36795891
|
|
ATM del
|
prostate cancer
|
sensitive
|
Berzosertib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, ATM-deficient prostate cancer cell lines were sensitive to treatment with Berzosertib (VX-970) in culture, demonstrating inhibition of cell growth (PMID: 32127357).
|
32127357
|
|
ATM del
|
prostate cancer
|
no benefit
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, ATM-deficient prostate cancer cell lines did not respond to treatment with Lynparza (olaparib) in culture (PMID: 32127357).
|
32127357
|
|
ATM del
|
prostate cancer
|
no benefit
|
Rucaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, ATM-deficient prostate cancer cell lines did not respond to treatment with Rubraca (rucaparib) in culture (PMID: 32127357).
|
32127357
|
|
ATM R3008C
|
pancreatic ductal adenocarcinoma
|
no benefit
|
Fluorouracil + Oxaliplatin + Veliparib
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial, Veliparib (ABT-888) in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) did not result in a clinical response in a patient with metastatic pancreatic ductal adenocarcinoma harboring ATM R3008C (PMID: 32669374; NCT01489865).
|
32669374
|
|
ATM T2333Nfs*40
|
pancreatic ductal adenocarcinoma
|
no benefit
|
Fluorouracil + Oxaliplatin + Veliparib
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial, Veliparib (ABT-888) in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) did not result in a clinical response in a patient with metastatic pancreatic ductal adenocarcinoma harboring ATM T2333Nfs*40 (reported as c.6997dupA) (PMID: 32669374; NCT01489865).
|
32669374
|
|
ATM inact mut
|
Advanced Solid Tumor
|
predicted - sensitive
|
Radiotherapy
|
Clinical Study |
Actionable |
In a clinical study, treatment with radiotherapy resulted in greater therapeutic efficacy in advanced solid tumor patients harboring an ATM inactivating mutation (n=177) compared to those who harbored an ATM variant of unknown significance (n=180), demonstrating a significantly decreased 2-year cumulative incidence of irradiated progression, 13.2% versus 27.5% (p=0.001), respectively, and the greatest clinical benefit was observed in tumors with bi-allelic ATM inactivating mutations (PMID: 32726432).
|
32726432
|
|
ATM negative
|
collecting duct carcinoma
|
predicted - sensitive
|
Elimusertib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment resulted in a partial response with a 69% decrease in tumor size in a patient with renal collecting duct carcinoma harboring ATM protein loss, treatment was ongoing at 385 days (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM I2629fs ATM neg
|
endometrial clear cell adenocarcinoma
|
predicted - sensitive
|
Elimusertib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment resulted in a partial response with a 53% decrease in tumor size in a patient with clear cell endometrial cancer harboring ATM I2629fs with ATM protein loss, treatment was ongoing at 433 days (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM T2333fs ATM neg
|
Her2-receptor negative breast cancer
|
predicted - sensitive
|
Elimusertib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment resulted in a partial response with a 54% decrease in tumor size in a patient with heavily treated, hormone receptor-positive, ERBB2 (HER2)-negative breast cancer harboring ATM T2333fs and ATM protein loss, who remained on treatment for 349 days (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM V1268fs
|
appendix cancer
|
predicted - sensitive
|
Elimusertib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Elimusertib (BAY1895344) treatment resulted in a partial response with a 35% decrease in tumor size in a patient with appendix cancer harboring ATM V1268fs, treatment was ongoing at 472 days (PMID: 32988960; NCT03188965).
|
32988960
|
|
ATM mutant
|
breast cancer
|
no benefit
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 4 patients with metastatic breast cancer harboring only germline mutations in ATM (PMID: 33119476; NCT03344965).
|
33119476
|
|
ATM inact mut
|
Advanced Solid Tumor
|
predicted - sensitive
|
Ceralasertib + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an overall response rate of 20% (1/5) and a clinical benefit rate of 40% (2/5) in patients with advanced solid tumors harboring ATM inactivating mutations, including a durable complete response in a patient with breast cancer and a durable stable disease in a patient with adenoid cystic carcinoma of minor salivary gland (PMID: 34527850; NCT02576444).
|
34527850
|
|
ATM P1069fs ATM LOH
|
salivary gland adenoid cystic carcinoma
|
predicted - sensitive
|
Ceralasertib + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing 22% reduction in target lesions in a patient with adenoid cystic carcinoma of minor salivary gland harboring germline ATM P1069fs with accompanying loss of heterozygosity (LOH), who remained on treatment for over 26 months (PMID: 34527850; NCT02576444).
|
34527850
|
|
ATM LOH ATM inact mut
|
estrogen-receptor positive breast cancer
|
predicted - sensitive
|
Ceralasertib + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing complete response for over 26 months in a patient with estrogen receptor-positive metastatic breast cancer harboring germline ATM mutation with accompanying loss of heterozygosity (LOH) (PMID: 34527850; NCT02576444).
|
34527850
|
|
ATM S1905Ifs*25
|
gallbladder carcinoma
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, treatment with Lynparza (olaparib) resulted in improved clinical symptoms and progression-free survival of 13 months in a patient with gallbladder carcinoma harboring ATM S1905Ifs*25 (PMID: 32045060).
|
32045060
|
|
ATM I1294Nfs*8 ATM E2977Rfs*2
|
colorectal adenocarcinoma
|
predicted - sensitive
|
Irinotecan + Olaparib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, Lynparza (olaparib) and Camptosar (irinotecan) combination treatment resulted in decreased tumor markers and stable disease in the primary and metastatic tumors in a heavily pretreated patient with metastatic colorectal adenocarcinoma harboring ATM E2977Rfs*2, ATM I1294Nfs*8, and KRAS G13D, lasting at least 4 months (PMID: 35004311).
|
35004311
|
|
ATM R3008H
|
esophagus small cell carcinoma
|
predicted - sensitive
|
Etoposide + Olaparib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, the combination of Lynparza (olaparib) and Vepesid (etoposide) resulted in a partial response and 5.9 months of progression-free survival in a patient with small cell esophageal carcinoma harboring ATM R3008H (PMID: 35480123).
|
35480123
|
|
ATM negative
|
stomach cancer
|
predicted - sensitive
|
Ceralasertib + Durvalumab
|
Phase II |
Actionable |
In a Phase II trial, Ceralasertib (AZD6738) and Imfinzi (durvalumab) combination therapy resulted in an overall response rate of 22.6% (7/31, all partial responses), disease control rate of 58.1%, and median progression-free survival (mPFS) of 3.0 mo in advanced gastric cancer patients, with improved mPFS (5.60 vs 1.65 mo; HR 0.13, p<0.001) in patients with ATM protein loss and/or homologous repair deficiency (HRD) compared to those with intact ATM expression or HR proficiency (PMID: 35790315; NCT03780608).
|
35790315
|
|
ATM R1882* ATM R3008H
|
pancreatic cancer
|
predicted - sensitive
|
Berzosertib + Irinotecan
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, the combination of Berzosertib (VX-970) and Camptosar (irinotecan) was tolerated in patients with advanced solid tumors, and resulted in a partial response that was ongoing at 11 months in a pancreatic cancer patient harboring ATM R3008H and germline ATM R1882* (J Clin Oncol 40, 2022 (suppl 16; abstr 3012); NCT02595931).
|
detail...
|
|
ATM S214fs
|
colorectal cancer
|
predicted - sensitive
|
Berzosertib + Irinotecan
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, the combination of Berzosertib (VX-970) and Camptosar (irinotecan) was tolerated in patients with advanced solid tumors, and resulted in a 26% tumor decrease lasting 7.5 months in a colorectal cancer patient harboring ATM S214fs (J Clin Oncol 40, 2022 (suppl 16; abstr 3012); NCT02595931).
|
detail...
|
|
ATM inact mut
|
Advanced Solid Tumor
|
predicted - sensitive
|
RP-3500
|
Phase Ib/II |
Actionable |
In a Phase I/II trial (TRESR), RP-3500 treatment resulted in an overall response rate (ORR) of 15% (7/46) and clinical benefit rate of 48% (22/46) in advanced solid tumor patients with ATM inactivation, an ORR of 18% (5/28) with germline ATM loss of function (LOF) mutations, and an ORR of 13% (2/15) with somatic ATM LOF mutations, with benefit in patients with non-small cell lung (n=2), bile duct (3/4), colorectal (3/6), and prostate (4/8) cancers (Ann Oncol (2024) 35 (Suppl_2): S496; NCT04497116).
|
detail...
|
|
ATM mutant
|
Advanced Solid Tumor
|
conflicting
|
Olaparib
|
Phase II |
Actionable |
In a Phase II trial (TAPUR), Lynparza (olaparib) treatment resulted in an objective response rate of 8% and a disease control rate of 25% (9/36, 1 complete response, 2 partial responses, 6 stable disease at 16+ weeks) in patients with advanced solid tumors harboring ATM mutations (Cancer Res 2022;82(12_Suppl):Abstract nr CT110; NCT02693535).
|
detail...
|
|
ATM mutant
|
Advanced Solid Tumor
|
conflicting
|
Olaparib
|
Phase II |
Actionable |
In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938).
|
detail...
|
|
ATM inact mut
|
transitional cell carcinoma
|
predicted - sensitive
|
Durvalumab + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (BAYOU), Lynparza (olaparib) and Imfinzi (durvalumab) improved median progression-free survival (5.6 vs 1.8 mo, HR 0.18) compared to Imfinzi (durvalumab) and placebo in a subgroup of patients with metastatic urothelial carcinoma harboring inactivating mutations in DNA damage repair genes (n=17), with 8.5% of the tumors harboring ATM inactivating mutations (PMID: 35737919; NCT03459846).
|
35737919
|
|
ATM del
|
prostate cancer
|
sensitive
|
PLX038
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, PLX038 resulted in inhibition of tumor growth and increased event-free survival in a cell line xenograft model of prostate cancer harboring ATM deletion (PMID: 35999657).
|
35999657
|
|
ATM del
|
prostate cancer
|
sensitive
|
PLX038 + Talazoparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, PLX038 and Talzenna (talazoparib) combination treatment resulted in synergistic inhibition of tumor growth and increased event-free survival in a cell line xenograft model of prostate cancer harboring ATM deletion (PMID: 35999657).
|
35999657
|
|
ATM Q1970*
|
breast ductal carcinoma
|
predicted - sensitive
|
PLX038 + Rucaparib
|
Case Reports/Case Series |
Actionable |
In a clinical trial, PLX038 and Rubraca (rucaparib) combination treatment resulted in a complete response within the first treatment cycle, followed by PLX038 monotherapy, which resulted in maintenance of tumor suppression for a total of 12 months in a patient with metastatic breast ductal carcinoma harboring germline ATM Q1970* (PMID: 35999657; NCT04209595).
|
35999657
|
|
ATM inact mut
|
Advanced Solid Tumor
|
no benefit
|
Avelumab + Talazoparib
|
Phase II |
Actionable |
In a Phase II trial (JAVELIN), Talzenna (talazoparib) and Bavencio (avelumab) combination therapy did not meet the prespecified futility requirement with a confirmed objective response rate of 4.9% (2/41, 2 partial responses) in patients with advanced solid tumors harboring ATM inactivating mutations, and subsequently, enrollment to the cohort was discontinued (PMID: 36394867; NCT03565991).
|
36394867
|
|
ATM Q628Pfs*7 ATM I1581Nfs*5 ATM A2843V
|
colon adenocarcinoma
|
sensitive
|
RP-3500
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, RP-3500 inhibited viability in a colon adenocarcinoma cell line harboring ATM Q628Pfs*7, ATM I1581Nfs*5, and ATM A2843V in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 34911817).
|
34911817
|
|
ATM Q1919P
|
lung non-small cell carcinoma
|
sensitive
|
RP-3500
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, RP-3500 inhibited viability in a non-small cell lung cancer cell line harboring ATM Q1919P in culture (PMID: 34911817).
|
34911817
|
|
ATM R2832C
|
mantle cell lymphoma
|
sensitive
|
RP-3500
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, RP-3500 inhibited viability in a mantle cell lymphoma cell line harboring ATM R2832C in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 34911817).
|
34911817
|
|
ATM loss
|
stomach cancer
|
sensitive
|
RP-3500
|
Preclinical - Pdx |
Actionable |
In a preclinical study, RP-3500 resulted in complete tumor regression in a gastric cancer patient-derived xenograft (PDX) model with biallelic loss of ATM (PMID: 34911817).
|
34911817
|
|
ATM R2832C
|
mantle cell lymphoma
|
sensitive
|
Niraparib + RP-3500
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, the combination of RP-3500 with Zejula (niraparib) inhibited tumor growth in a mantle cell lymphoma cell line xenograft model harboring ATM R2832C (PMID: 34911817).
|
34911817
|
|
ATM N2875H
|
prostate cancer
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (TOPARP-A), Lynparza (olaparib) treatment resulted in a conversion in the circulating tumor-cell count and an 85% decrease in PSA level in a patient with metastatic castration-resistant prostate cancer harboring ATM N2875H (PMID: 26510020; NCT01682772).
|
26510020
|
|
ATM V2288fs
|
prostate cancer
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (TOPARP-A), Lynparza (olaparib) treatment resulted in a conversion in the circulating tumor-cell count, a 29% decrease in PSA level, and radiologic stable disease in a patient with metastatic castration-resistant prostate cancer harboring ATM V2288fs (PMID: 26510020; NCT01682772).
|
26510020
|
|
ATM R1882*
|
gastroesophageal adenocarcinoma
|
predicted - sensitive
|
Capecitabine + Oxaliplatin
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, treatment with the combination of Xeloda (capecitabine) and Eloxatin (oxaliplatin) resulted in a partial response and a progression-free survival of 12.3 months in a patient with gastroesophageal adenocarcinoma harboring ATM R1882* (PMID: 37129948).
|
37129948
|
|
ATM W1058* ATM S1993fs
|
gastroesophageal adenocarcinoma
|
predicted - sensitive
|
Fluorouracil + Leucovorin + Oxaliplatin
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, treatment with the combination of Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) resulted in a partial response and a progression-free survival of 7.2 months in a patient with gastroesophageal adenocarcinoma harboring ATM W1058* and S1993fs (PMID: 37129948).
|
37129948
|
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Enzalutamide + Talazoparib
|
FDA approved |
Actionable |
In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including ATM, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197).
|
detail...
37285865
|
|
ATM inact mut
|
prostate cancer
|
sensitive
|
Enzalutamide + Talazoparib
|
Guideline |
Actionable |
Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATM mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org).
|
detail...
|
|
ATM Q1331H ATM I1441fs
|
lung non-small cell carcinoma
|
predicted - sensitive
|
Radiotherapy
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, radiotherapy treatment resulted in 3.1 months of local disease control and no in-field recurrence in a patient with non-small cell lung cancer harboring ATM I1441fs and Q1331H (PMID: 28055970).
|
28055970
|
|
ATM R1875*
|
colon cancer
|
predicted - sensitive
|
Radiotherapy
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, radiotherapy treatment resulted in 3.8 months of local disease control and no in-field recurrence in a patient with colon cancer harboring ATM R1875* (PMID: 28055970).
|
28055970
|
|
ATM R1898*
|
colon cancer
|
predicted - sensitive
|
Radiotherapy
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, radiotherapy treatment resulted in 3.9 months of local disease control and no in-field recurrence in a patient with colon cancer harboring ATM R1898* (PMID: 28055970).
|
28055970
|
|
ATM L2738*
|
thyroid cancer
|
predicted - sensitive
|
Radiotherapy
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, radiotherapy treatment resulted in 5.16 months of local disease control and no in-field recurrence in a patient with thyroid cancer harboring ATM L2738* (PMID: 28055970).
|
28055970
|
|
ATM I1453fs
|
tongue squamous cell carcinoma
|
predicted - sensitive
|
Radiotherapy
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, radiotherapy treatment resulted in a complete metabolic response lasting at least 34 months in a patient with squamous cell carcinoma of the tongue, and the patient was found to harbor ATM I1453fs (PMID: 28055970).
|
28055970
|
|
ATM R3008H
|
prostate cancer
|
predicted - sensitive
|
RP-3500
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial (TRESR), RP-3500 treatment resulted in a 29% tumor reduction in a castration-resistant prostate cancer patient harboring ATM R3008H, who remained on treatment for more than 61 weeks (PMID: 37277454; NCT04497116).
|
37277454
|
|
ATM inact mut
|
Advanced Solid Tumor
|
no benefit
|
Ipilimumab + Nivolumab
|
Phase II |
Actionable |
In a Phase II trial (TAPUR), Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment did not meet predetermined efficacy criteria in patients with advanced solid tumors harboring ATM mutations, resulting in an objective response rate of 14% (4/29, 1 complete and 3 partial responses), a disease control rate of 24% (7/29), with stable disease of at least 16 weeks in 3 patients, a median progression-free survival of 9 weeks, and median overall survival of 28 weeks (PMID: 38039429; NCT02693535).
|
38039429
|
|
ATM loss
|
triple-receptor negative breast cancer
|
predicted - sensitive
|
Ceralasertib + Olaparib
|
Phase II |
Actionable |
In a Phase II trial (plasmaMATCH), treatment with the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in limited efficacy in patients with advanced triple-negative breast cancer, with an objective response rate of 17.1% (12/70), but in patients with wild-type BRCA1/2 and ATM loss, resulted in a median progression-free survival of 3.4 vs 2.5 mo and response rate of 21.4 (3/14) vs 13.8% (4/29) in patients without loss of ATM (PMID: 37773077; NCT03182634).
|
37773077
|
|
ATM inact mut
|
lung non-small cell carcinoma
|
predicted - sensitive
|
Ceralasertib + Durvalumab
|
Phase II |
Actionable |
In a Phase II trial (HUDSON), treatment with the combination of Imfinzi (durvalumab) and Ceralasertib (AZD6738) demonstrated efficacy in patients with advanced non-small cell lung cancer harboring inactivating ATM mutations, with an objective response rate of 26.1% (6/23, all partial responses), a median progression-free survival of 8.4 months, and a median overall survival of 22.8 months (PMID: 38351187; NCT03334617).
|
38351187
|
|
ATM del
|
breast cancer
|
predicted - sensitive
|
Radiotherapy + RP-3500
|
Preclinical |
Actionable |
In a preclinical study, RP-3500 and radiotherapy synergistically inhibited growth of an ATM knockout mouse breast cancer cell line in culture, delayed tumor growth (p<0.001), and improved survival (20% vs 0% alive at 150 days) in a mouse syngeneic model (Cancer Res (2024) 84 (1_Supplement): A002).
|
detail...
|
|
ATM del
|
colon cancer
|
predicted - sensitive
|
Radiotherapy + RP-3500
|
Preclinical |
Actionable |
In a preclinical study, RP-3500 and radiotherapy synergistically inhibited growth of an ATM knockout mouse colon cancer cell line in culture and improved survival in a mouse syngeneic model, with complete responses achieved in 7 out of 8 ATM knockout mice compared to 1 out of 8 ATM wild-type mice (Cancer Res (2024) 84 (1_Supplement): A002).
|
detail...
|
|
ATM inact mut
|
Advanced Solid Tumor
|
predicted - sensitive
|
Radiotherapy + RP-3500
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, the addition of RP-3500 to radiotherapy treatment resulted in metabolic complete responses in two patients with advanced solid tumors harboring ATM inactivating mutations (Cancer Res (2024) 84 (1_Supplement): A002, NCT05566574).
|
detail...
|
|
ATM E473* ATM loss
|
lung adenocarcinoma
|
sensitive
|
ART0380
|
Preclinical - Pdx |
Actionable |
In a preclinical study, ART0380 induced tumor regression in a lung adenocarcinoma patient-derived xenograft (PDX) model harboring ATM E473* with loss of Atm expression (PMID: 38416404).
|
38416404
|
|
ATM S214Ffs*40 ATM loss
|
colorectal cancer
|
sensitive
|
ART0380
|
Preclinical - Pdx |
Actionable |
In a preclinical study, ART0380 inhibited tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring ATM S214Ffs*40 with loss of Atm expression (PMID: 38416404).
|
38416404
|
|
ATM S214Pfs*16
|
colorectal cancer
|
sensitive
|
ART0380
|
Preclinical - Pdx |
Actionable |
In a preclinical study, ART0380 inhibited tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring ATM S214Pfs*16 (PMID: 38416404).
|
38416404
|
|
ATM M779I
|
colorectal cancer
|
sensitive
|
ART0380
|
Preclinical - Pdx |
Actionable |
In a preclinical study, ART0380 inhibited tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring ATM M779I (PMID: 38416404).
|
38416404
|
|
ATM dec exp ATM inact mut
|
mantle cell lymphoma
|
predicted - sensitive
|
ART0380
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, ART0380 inhibited cell growth of a mantle cell lymphoma cell line with an inactivating ATM mutation and decreased Atm expression in culture and inhibited tumor growth in a cell line xenograft model (PMID: 38416404).
|
38416404
|
|
ATM inact mut
|
Advanced Solid Tumor
|
no benefit
|
Ceralasertib
|
Phase II |
Actionable |
In a Phase IIa trial (PLANETTE), Ceralasertib (AZD6738) treatment demonstrated manageable safety but limited efficacy in patients with advanced solid tumors excluding non-small cell lung cancer harboring ATM mutations and/or loss of ATM protein expression (n=30), resulting in an objective response rate of 7.1% (2/28, 1 complete and 1 partial response) (Cancer Res (2024) 84 (7_Supplement): CT222; NCT04564027).
|
detail...
|
|
ATM inact mut
|
prostate cancer
|
no benefit
|
Ceralasertib
|
Phase II |
Actionable |
In a Phase IIa trial (PLANETTE), Ceralasertib (AZD6738) treatment demonstrated manageable safety but limited efficacy in patients with metastatic castration-resistant prostate cancer harboring ATM mutations and/or ATM loss (n=15), with a composite response rate of 7.7% (1/13) in patients with confirmed ATM mutations (Cancer Res (2024) 84 (7_Supplement): CT222; NCT04564027).
|
detail...
|
|
ATM negative
|
prostate cancer
|
no benefit
|
Ceralasertib
|
Phase II |
Actionable |
In a Phase IIa trial (PLANETTE), Ceralasertib (AZD6738) treatment demonstrated manageable safety but limited efficacy in patients with metastatic castration-resistant prostate cancer harboring ATM mutations and/or loss of ATM protein expression (n=15), resulting in a composite response rate of 7.7% (1/13) (Cancer Res (2024) 84 (7_Supplement): CT222; NCT04564027).
|
detail...
|
|
ATM negative
|
Advanced Solid Tumor
|
no benefit
|
Ceralasertib
|
Phase II |
Actionable |
In a Phase IIa trial (PLANETTE), Ceralasertib (AZD6738) treatment demonstrated manageable safety but limited efficacy in patients with advanced solid tumors excluding non-small cell lung cancer harboring ATM mutations and/or loss of ATM protein expression (n=30), resulting in an objective response rate of 7.1% (2/28, 1 complete and 1 partial response) (Cancer Res (2024) 84 (7_Supplement): CT222; NCT04564027).
|
detail...
|
|
ATM mutant
|
breast cancer
|
not applicable
|
N/A
|
Guideline |
Risk Factor |
Germline ATM mutations are associated with increased risk of developing breast cancer (NCCN.org).
|
detail...
|
|
ATM inact mut
|
prostate cancer
|
no benefit
|
unspecified PARP inhibitor
|
Clinical Study - Meta-analysis |
Actionable |
In a combined analysis of 6 clinical trials, PARP inhibitor therapy did not benefit patients with metastatic castration-resistant prostate cancer harboring ATM mutations compared to placebo, with an HR of 1.05 (19 vs 19 mo) for radiographic progression-free survival and 1.18 (33 vs 33 mo) for overall survival when combined with AR pathway inhibitors, and an objective response rate of 7% (5/70) as monotherapy (PMID: 38484203; NCT02987543, NCT03732820, NCT03395197, NCT03748641, NCT02952534, NCT03148795).
|
38484203
|
|
ATM mutant
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lung non-small cell carcinoma
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predicted - sensitive
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M1774
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Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, M1774 inhibited tumor growth in a cell line xenograft model of non-small cell lung cancer harboring an ATM mutation (PMID: 38407317).
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38407317
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ATM mutant
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ovarian cancer
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not applicable
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N/A
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Guideline |
Risk Factor |
Germline ATM mutations are associated with increased risk of developing ovarian cancer (NCCN.org).
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detail...
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ATM mutant
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pancreatic cancer
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not applicable
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N/A
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Guideline |
Risk Factor |
Germline ATM mutations are associated with increased risk of developing pancreatic cancer (NCCN.org).
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detail...
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ATM del
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colorectal cancer
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sensitive
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E7820
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, E7820 inhibited viability of a colorectal cancer cell line with knockout of ATM in culture (PMID: 38789724).
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38789724
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ATM del
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colorectal cancer
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sensitive
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Indisulam
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Preclinical - Cell culture |
Actionable |
In a preclinical study, Indisulam (E7070) inhibited viability of a colorectal cancer cell line with knockout of ATM in culture (PMID: 38789724).
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38789724
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ATM inact mut
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Advanced Solid Tumor
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sensitive
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Irinotecan + Rucaparib
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Phase I |
Actionable |
In a Phase I trial, Rubraca (rucaparib) and Camptosar (irinotecan) combination therapy was well tolerated and resulted in a clinical benefit rate of 35% (6/17, 2 partial responses, 4 stable diseases over 6 months) in patients with advanced solid tumors harboring BRCA1 (n=3), BRCA2 (n=4), PALB2 (n=1), or ATM (n=11) mutations, including partial responses in a patient with PALB2-mutated peritoneal carcinoma and in a patient with ATM-mutated small bowel carcinoma (PMID: 38865673; NCT03318445).
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38865673
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ATM S1599*
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appendix cancer
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predicted - sensitive
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Talazoparib
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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).
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39085400
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ATM G1676fs
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cholangiocarcinoma
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predicted - sensitive
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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).
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39085400
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ATM inact mut
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Advanced Solid Tumor
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predicted - sensitive
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Durvalumab + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, treatment with the combination of Lynparza (olaparib) and Imfinzi (durvalumab) led to a 6-month progression-free survival (PFS) rate of 35%, objective tumor response (OTR) rate of 19% (3/16, all partial responses (PR)), and median PFS of 3.7mo in advanced solid tumor patients harboring BRCA1/2 mutations and a 6-month PFS rate of 38%, OTR rate of 9% (3/32, 1 complete, 2 PR), and median PFS of 3.6mo with other HRR alterations, including ATM (n=9) and CHEK2 (n=3) (PMID: 37365284).
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37365284
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ATM inact mut
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invasive ductal carcinoma
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predicted - sensitive
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Durvalumab + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, treatment with the combination of Lynparza (olaparib) and Imfinzi (durvalumab) resulted in a partial response in a patient with invasive ductal carcinoma harboring an ATM inactivating mutation (PMID: 37365284).
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37365284
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ATM inact mut
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neuroendocrine carcinoma
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predicted - sensitive
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Durvalumab + Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial, treatment with the combination of Lynparza (olaparib) and Imfinzi (durvalumab) resulted in a partial response in a patient with a neuroendocrine carcinoma harboring an ATM inactivating mutation (PMID: 37365284).
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37365284
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ATM inact mut
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pancreatic cancer
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predicted - sensitive
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RP-3500
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial (TRESR), RP-3500 treatment resulted in a partial response at week 54 in a patient with advanced pancreatic cancer harboring a germline ATM frameshift mutation (PMID: 37277454; NCT04497116).
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37277454
|
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ATM inact mut
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lung non-small cell carcinoma
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predicted - sensitive
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RP-3500
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial (TRESR), RP-3500 treatment resulted in a partial response after 37 weeks of treatment in a patient with advanced non-small cell lung cancer harboring germline biallelic ATM inactivation (PMID: 37277454; NCT04497116).
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37277454
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ATM inact mut
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prostate cancer
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sensitive
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Abiraterone + Olaparib + Prednisone
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (BRCAAway), Zytiga (abiraterone), Adason (prednisone), and Lynparza (olaparib) first-line combination treatment led to an objective response rate of 33% (7/21) and improved median progression-free survival compared to olaparib (39 mo vs 14 mo, HR=0.37) or the combination of abiraterone and prednisone (39 mo vs 8.6 mo, HR=0.33) in patients with metastatic castration-resistant prostate cancer harboring BRCA1 (n=3), BRCA2 (n=46) or ATM (n=11) mutations (PMID: 39115414; NCT03012321).
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39115414
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ATM mutant
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chronic lymphocytic leukemia/small lymphocytic lymphoma
|
not applicable
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N/A
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Guideline |
Prognostic |
ATM mutations are associated with shorter time to first treatment, progression-free survival, time to next treatment, and overall survival with chemoimmunotherapy compared to wild-type ATM in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org).
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detail...
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