Molecular Profile Detail

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Profile Name ATM inact mut
Gene Variant Detail

ATM inact mut (loss of function)

Relevant Treatment Approaches Olaparib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
ATM inact mut mantle cell lymphoma sensitive Olaparib 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 prostate cancer predicted - sensitive Abiraterone + Niraparib + Prednisone Phase III Actionable In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) significantly improved radiographic progression-free survival (16.5 vs 13.7 mo, HR 0.73, p=0.0217) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring alterations in homologous recombination repair genes including ATM, BRCA1/2, BRIP1, CHEK2, FANCA, HDAC2, and PALB2 (J Clin Oncol 40, 2022 (suppl 6; abstr 12); NCT03748641). detail...
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 prostate cancer sensitive Olaparib Olaparib Phase II Actionable In a Phase II clinical trial, 80% (4/5) of metastatic, castration-resistant prostate cancer patients harboring an ATM inactivating mutation responded to Lynparza (olaparib) (PMID: 26510020). 26510020
ATM inact mut prostate cancer sensitive Olaparib Olaparib Phase II Actionable In a Phase II (TOPARP-B) trial, 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 Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment improved progression-free survival (7.4 vs 3.6 mo, HR=0.34, p<0.001), objective response rate (33%, 28/84 vs 2%, 1/43, OR=20.86, p<0.001), and median time to pain progression (HR=0.44, p=0.02) compared to control in patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious mutations in BRCA1/2 or ATM who progressed on hormone therapy (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM inact mut prostate cancer sensitive Olaparib 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 inact mut lymphoid leukemia sensitive Olaparib 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 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 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 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 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 chronic lymphocytic leukemia sensitive Olaparib 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 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 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 inact mut Advanced Solid Tumor predicted - sensitive BAY1895344 Phase I Actionable In a Phase I trial, 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 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT03570476 Phase II Olaparib Olaparib Before Surgery in Treating Participants With Localized Prostate Cancer Terminated USA 0
NCT04336943 Phase II Durvalumab + Olaparib Durvalumab and Olaparib for the Treatment of Prostate Cancer in Men Predicted to Have a High Neoantigen Load Recruiting USA 0
NCT04983745 Phase II Dostarlimab-gxly + Niraparib Niraparib and Dostarlimab in HRD Solid Tumors (DIDO) Not yet recruiting USA 0
NCT02278250 Phase I VX-803 Carboplatin + VX-803 An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M4344 (Formerly VX-803) as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors Completed USA | ESP 2
NCT04053322 Phase II Durvalumab + Fulvestrant + Olaparib Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (DOLAF) Recruiting FRA 0
NCT03188965 Phase I BAY1895344 First-in-human Study of ATR Inhibitor BAY1895344 in Patients With Advanced Solid Tumors and Lymphomas Active, not recruiting USA | CAN 5
NCT03344965 Phase II Olaparib Olaparib In Metastatic Breast Cancer Recruiting USA 0
NCT02952534 Phase II Rucaparib A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON2) Completed USA | ITA | FRA | ESP | DEU | CAN | BEL 5
NCT03565991 Phase II Avelumab + Talazoparib Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors Active, not recruiting USA | ITA | FRA | ESP | BEL 4
NCT02734004 Phase Ib/II Durvalumab + Olaparib Bevacizumab + Durvalumab + Olaparib A Phase I/II Study of MEDI4736 in Combination With Olaparib in Patients With Advanced Solid Tumors. (MEDIOLA) Completed USA | FRA 5
NCT03601923 Phase II Niraparib Niraparib in Patients With Pancreatic Cancer Recruiting USA 0
NCT04253262 Phase Ib/II Copanlisib + Rucaparib A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer Recruiting USA 0
NCT05071209 Phase Ib/II BAY1895344 Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors Recruiting USA 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
NCT02975934 Phase III Rucaparib Docetaxel Enzalutamide Abiraterone A Study of Rucaparib Versus Physician's Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON3) Active, not recruiting USA | ITA | FRA | ESP | DEU | CAN | BEL 5
NCT02264678 Phase Ib/II Ceralasertib Carboplatin + Ceralasertib Ceralasertib + Durvalumab Ceralasertib + Olaparib Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents Recruiting USA | FRA 2
NCT03840967 Phase II Niraparib A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma Recruiting USA 0
NCT05188508 Phase II Olaparib + Pembrolizumab + Temozolomide Pembrolizumab, Olaparib, and Temozolomide for People With Glioma Recruiting USA 0
NCT04550494 Phase II Talazoparib Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations Recruiting USA 0
NCT05038839 Phase I Cabozantinib + Pamiparib Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors Recruiting USA 0
NCT03786796 Phase II Olaparib Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (ORCHID) Recruiting USA 0
NCT04985721 Phase II Pamiparib + Tislelizumab A Trial of Pamiparib With Tislelizumab in Patients With Advanced Tumours With Homologous Recombination Repair Defects (IMPARP-HRD) Recruiting 1
NCT04824937 Phase II Talazoparib + Telaglenastat Telaglenastat + Talazoparib In Prostate Cancer Not yet recruiting USA 0
NCT03047135 Phase II Olaparib Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis Recruiting USA 0
NCT03810105 Phase II Durvalumab + Olaparib A Study of Olaparib and Durvalumab in Prostate Cancer Active, not recruiting USA 0
NCT05011383 Phase II Testosterone High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT) Recruiting USA 0
NCT02401347 Phase II Talazoparib Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors Recruiting USA 0
NCT05033756 Phase II Olaparib + Pembrolizumab Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (COMPRENDO) Not yet recruiting DEU 0
NCT03442556 Phase II Carboplatin + Docetaxel + Rucaparib Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency Recruiting USA 0
NCT04266912 Phase Ib/II Avelumab + Berzosertib Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors 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
NCT03209401 Phase I Carboplatin + Niraparib Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies Recruiting USA 0
NCT03233204 Phase II Olaparib Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial) Active, not recruiting USA 1
NCT04564027 Phase II Ceralasertib A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer Recruiting USA | FRA | ESP 0
NCT04826341 Phase Ib/II Berzosertib + Sacituzumab govitecan-hziy A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors Recruiting USA 0
NCT05010096 Phase I BAY1895344 + Copanlisib BAY1895344 and Copanlisib for the Treatment of Molecularly Selected Patients With Advanced Solid Tumors Not yet recruiting USA 0
NCT04276376 Phase II Atezolizumab + Rucaparib Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (ARIANES) Recruiting FRA 0
NCT04666740 Phase II Olaparib + Pembrolizumab A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy Recruiting USA 0