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|Protein Effect||loss of function|
|Gene Variant Descriptions||ATM negative indicates a lack of expression of the ATM mRNA and/or protein.|
|Associated Drug Resistance|
|Category Variants Paths||
ATM mutant ATM inact mut ATM negative
|Molecular Profile||Indication/Tumor Type||Response Type||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||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 negative||collecting duct carcinoma||predicted - sensitive||BAY1895344||Case Reports/Case Series||Actionable||In a Phase I trial, 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|