{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:12:27Z","timestamp":1784650347886,"version":"3.55.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Preclinical studies suggest the combination of the poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) inhibitor olaparib and the ataxia telangiectasia\u2013mutated and Rad3-related (ATR) inhibitor ceralasertib has synergistic antitumor activity in homologous recombination proficient (HRP) and homologous recombination repair gene mutation (HRRm) patients. This study aims to determine the efficacy of olaparib plus ceralasertib in metastatic castration-resistant prostate cancer (mCRPC) with and without HRRm.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>PATIENTS AND METHODS<\/jats:title>\n            <jats:p>\n              Thirty-five HRP and 12 HRRm PARP inhibitor\u2013na\u00efve patients with mCRPC progressing on \u22651 line of therapy or previous androgen receptor pathway inhibitor were enrolled. Patients received olaparib (300 mg twice daily) and ceralasertib (160 mg once daily, days 1-7) in 28-day cycles. HRRm was defined as biallelic inactivation of\n              <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n              or\n              <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n              , monoallelic inactivation of\n              <jats:italic toggle=\"yes\">ATM<\/jats:italic>\n              , or germline inactivation of any of these genes. The primary end point was disease response rate (dRR; confirmed prostate-specific antigen decline \u226550% and\/or complete\/partial radiographic response by RECIST v1.1) in HRP patients. Secondary end points included dRR in HRRm patients, progression-free survival (PFS), and safety\/toxicity. Two-stage designs were used.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>Four of 35 (11%; 95% CI, 3.2 to 26.7) HRP and four of 12 HRRm patients responded. Median PFS was 8.2 months (95% CI, 5.3 to not reached) for HRP patients. Thirty-six percent of patients had \u2265grade 3 toxicity, most commonly from anemia. Limitations include small, single-arm, nonrandomized trial design.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Combining ceralasertib with olaparib had limited activity in patients with HRP mCRPC. HRRm response rate was not greater than previous single-agent PARP inhibitor clinical trials.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-25-00457","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:59:28Z","timestamp":1758052768000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Multicenter Phase II Study of Olaparib and the ATR Inhibitor Ceralasertib in Metastatic Castration-Resistant Prostate Cancer (TRAP)"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-8659","authenticated-orcid":true,"given":"Irene","family":"Tsung","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology and Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-988X","authenticated-orcid":false,"given":"David 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