{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:36:22Z","timestamp":1791923782691,"version":"4.3.4"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>Nonclinical studies suggest that the combination of poly(ADP-ribose) polymerase and programmed cell death 1\/programmed cell death\u2013ligand 1 inhibitors has enhanced antitumor activity; however, the patient populations that may benefit from this combination have not been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate whether the combination of avelumab and talazoparib is effective in patients with pathogenic <jats:italic>BRCA1\/2<\/jats:italic> or <jats:italic>ATM<\/jats:italic> alterations, regardless of tumor type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In this pan-cancer tumor-agnostic phase 2b nonrandomized controlled trial, patients with advanced <jats:italic>BRCA1\/2-<\/jats:italic>altered or <jats:italic>ATM<\/jats:italic>-altered solid tumors were enrolled into 2 respective parallel cohorts. The study was conducted from July 2, 2018, to April 12, 2020, at 42 institutions in 9 countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Patients received 800 mg of avelumab every 2 weeks and 1 mg of talazoparib once daily.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary end point was confirmed objective response (OR) per RECIST 1.1 by blinded independent central review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 200 patients (median [range] age, 59.0 [26.0-89.0] years; 132 [66.0%] women; 15 [7.5%] Asian, 11 [5.5%] African American, and 154 [77.0%] White participants) were enrolled: 159 (79.5%) in the <jats:italic>BRCA1\/2<\/jats:italic> cohort and 41 (20.5%) in the <jats:italic>ATM<\/jats:italic> cohort. The confirmed OR rate was 26.4% (42 patients, including 9 complete responses [5.7%]) in the <jats:italic>BRCA1\/2<\/jats:italic> cohort and 4.9% (2 patients) in the <jats:italic>ATM<\/jats:italic> cohort. In the <jats:italic>BRCA1\/2<\/jats:italic> cohort, responses were more frequent (OR rate, 30.3%; 95% CI, 22.2%-39.3%, including 8 complete responses [6.7%]) and more durable (median duration of response: 10.9 months [95% CI, 6.2 months to not estimable]) in tumor types associated with increased heritable cancer risk (ie, <jats:italic>BRCA1\/2<\/jats:italic>-associated cancer types, such as ovarian, breast, prostate, and pancreatic cancers) and in uterine leiomyosarcoma (objective response in 3 of 3 patients and with ongoing responses greater than 24 months) compared with non\u2013<jats:italic>BRCA<\/jats:italic>-associated cancer types. Responses in the <jats:italic>BRCA1\/2<\/jats:italic> cohort were numerically higher for patients with tumor mutational burden of 10 or more mutations per megabase (mut\/Mb) vs less than 10 mut\/Mb. The combination was well tolerated, with no new safety signals identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this phase 2b nonrandomized controlled trial, neither the <jats:italic>BRCA1\/2<\/jats:italic> nor <jats:italic>ATM<\/jats:italic> cohort met the prespecified OR rate of 40%. Antitumor activity for the combination of avelumab and talazoparib in patients with <jats:italic>BRCA1\/2<\/jats:italic> alterations was observed in some patients with <jats:italic>BRCA1\/2<\/jats:italic>-associated tumor types and uterine leiomyosarcoma; benefit was minimal in non\u2013<jats:italic>BRCA<\/jats:italic>-associated cancer types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03565991\">NCT03565991<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.5218","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T16:01:25Z","timestamp":1668700885000},"page":"29","source":"Crossref","is-referenced-by-count":63,"title":["Avelumab Plus Talazoparib in Patients With <i>BRCA1\/2<\/i>- or <i>ATM<\/i>-Altered Advanced Solid Tumors"],"prefix":"10.1001","volume":"9","author":[{"given":"Alison M.","family":"Schram","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Colombo","sequence":"additional","affiliation":[{"name":"University of Milan-Bicocca and Istituto Europeo di Oncologia, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Arrowsmith","sequence":"additional","affiliation":[{"name":"Tennessee Oncology\/Sarah Cannon Research Institute, Chattanooga"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Narayan","sequence":"additional","affiliation":[{"name":"Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Yonemori","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital, Chuo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Scambia","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. 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