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The phase 2 POLAR trial evaluated maintenance pembrolizumab plus olaparib following platinum-based chemotherapy in biomarker-stratified metastatic PC. Sixty-three participants were enrolled into three cohorts: cohort A (\n                    <jats:italic>BRCA1<\/jats:italic>\n                    \/\n                    <jats:italic>BRCA2<\/jats:italic>\n                    -mutated or\n                    <jats:italic>PALB2<\/jats:italic>\n                    -mutated HRD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933), cohort B (non-core HRD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915) and cohort C (platinum sensitive, HRD-wild type,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915). Cohort A used a two-stage design with co-primary endpoints of at least 43% Response Evaluation Criteria in Solid Tumors (RECIST) objective response rate (ORR) and at least 77% 6-month progression-free survival (PFS) rate. Among RECIST-evaluable participants in cohort A (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920), ORR was 35% (95% confidence interval (CI): 15\u221259%), whereas 6-month PFS rate in the full cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933) was 64% (95% CI: 49\u221282%), not meeting the primary endpoint. At a median follow-up of 37\u2009months (95% CI: 27\u221247), median PFS and overall survival (OS) for cohort A were 8.3 (95% CI: 5.3\u2212not reached (NR)) and 28 (95% CI: 12\u2212NR) months, with 2-year and 3-year OS rates of 56% (95% CI: 41\u221276%) and 44% (95% CI: 28\u221269%), respectively. In cohorts B and C, ORR was 8% (95% CI: 0\u221238%) and 14% (95% CI: 2%-43%); median PFS was 4.8 (95% CI: 4.0\u221212) and 3.3 (95% CI: 1.9\u22124.8) months; and median OS was 18 (95% CI: 13\u2212NR) and 10 (95% CI: 8.9\u221224) months, respectively. Preplanned translational analyses showed that circulating tumor DNA response, increased tumor-infiltrating lymphocytes and enrichment of frameshift indel neoantigens were associated with durable clinical benefit. These data suggest that a subset of HRD PC may derive prolonged benefit from PARP-ICB maintenance and support further development of biomarker-guided precision immunotherapy strategies in PC. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/study\/NCT04666740\" ext-link-type=\"uri\">NCT04666740<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04299-5","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T10:02:42Z","timestamp":1774432962000},"page":"1783-1793","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR 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M.H. reports honoraria from Pierre Fabre, AstraZeneca, Amgen and Viatris; research funding from Servier; and travel support from Astellas. M.A.P. reports stock ownership in Amgen (former employee). A.M.V. reports that her spouse consults for AstraZeneca and Paige.AI and that she holds intellectual property rights with SOPHiA Genetics. K.H.Y. reports a relationship with Ipsen Pharma. D.R. reports consulting for Boston Scientific and equity interests (self and\/or spouse) in Eli Lilly, Novartis, Bristol Myers Squibb, Merck, Abbott Laboratories, Pfizer, UnitedHealth Group, Johnson & Johnson, CVS Health, Sanofi, Elevance Health, GlaxoSmithKline, Haleon, Sandoz, Procter & Gamble and others as well as uncompensated professional service for the\n                      Journal of Oncology Practice\n                      ,\n                      Cancer Medicine\n                      and the American Board of Internal Medicine. M.B.F. has served on advisory boards for Bristol Myers Squibb, Intera, Genzyme and Abbott Laboratories. J.J.H. reports consulting relationships with Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Cogent, Elevar, Exelixis, Eisai, Merck, Rayze Bio, Servier and Jazz Pharmaceuticals and research support from AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Incyte, Jazz Pharmaceuticals, Kinnate, Tvardi and Zymeworks. A.S.E. reports royalties from UpToDate. D.K. reports consulting for Bristol Myers Squibb, BeiGene, GlaxoSmithKline, Guardant Health, Johnson & Johnson and Merck. J.D.S. reports consulting for Hoplite Healthcare and advisory roles with Open Evidence. H.Z. reports relationships with Revolution Medicines and Eli Lilly. M.S. reports consulting for Boston Scientific. N.R. reports research funding from Pfizer. V.B. reports relationships with Genentech, Merck and AbbVie. D.P. serves on the scientific advisory board of Insitro. C.A.I.-D. reports research funding and advisory roles with Bristol Myers Squibb and Episteme. E.M.O. reports research funding to the institution from Arcus, Genentech\/Roche, BioNTech, AstraZeneca, Elicio Therapeutics, Digestive Care, Agenus, Amgen, Revolution Medicines and Tango Therapeutics; uncompensated advisory or data safety monitoring board roles with Arcus, Amgen, AstraZeneca, Cantargia, BridgeBio, Oncolytics, Alligator BioSciences, Pfizer, Agenus, BioNTech, Ipsen, Ikena, Merck, Immuneering, Moma Therapeutics, Novartis, Astellas, Bristol Myers Squibb, Revolution Medicines, Regeneron and Tango Therapeutics; and travel support from BioNTech and Arcus. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}