Molecular Profile Detail

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Profile Name ATM negative
Gene Variant Detail

ATM negative (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 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 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 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 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 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...