Abstract CT004: KEYLYNK-007: Tumor agnostic trial of olaparib plus pembrolizumab in homologous recombination repair mutation- and homologous recombination deficiency- positive advanced cancers

Abstract Background: Early data suggest poly (ADP-ribose) polymerase inhibitor (PARPi)/anti-PD-[L]1 synergy in homologous recombination repair-mutated (HRRm) or homologous recombination deficient (HRD) cancers. KEYLYNK-007 (NCT04123366) is a tumor-agnostic trial that evaluated the PARPi olaparib plus pembrolizumab in HRRm/HRD advanced tumors. Methods: This phase 2 trial enrolled participants (pts) with HRRm or HRD+ advanced solid tumors to 3 cohorts: BRCAm (except breast and ovarian), non-BRCA HRRm, and non-HRRm HRD. HRRm/HRD was centrally confirmed using the Lynparza HRR-HRD Assay before treatment with 300 mg olaparib BID + 200 mg pembrolizumab Q3W (≤35 cycles). Primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were duration of response and PFS per RECIST 1.1 by central review, OS, and safety. Results: At data cutoff (May 16, 2024), 332 pts were enrolled (n = 132 [BRCAm], n = 104 [non-BRCA HRRm], n = 96 [non-HRRm HRD]) (Table). Median follow-up was 13.4 (BRCAm), 10.4 (non-BRCA HRRm), and 10.8 months (non-HRRm HRD). ORR was 27% (BRCAm), 12% (non-BRCA HRRm), and 12% (non-HRRm HRD). Confirmed RECIST 1.1 responders beyond PARPi-approved indications included pts with advanced breast, ovarian, pancreatic, urothelial, renal, biliary, cervical, esophageal SCC, CRC, gastroesophageal adenocarcinoma, duodenal, small intestine, thyroid, salivary gland, HNSCC, NSCLC, SCLC, leiomyosarcoma, and other sarcomas. There were also multiple responses in HRRm prostate cancer. Grade ≥3 drug-related adverse events occurred in 30% pts; 1/332 (0.3%) pt died from septic shock. Conclusions: In this tumor-agnostic trial, olaparib plus pembrolizumab showed promising durable antitumor activity and manageable safety in HRRm and HRD+ (particularly BRCAm) advanced cancers beyond currently approved indications. Biomarker analysis is ongoing for other predictive biomarkers of response. Citation Format: Timothy A. Yap, Ronnie Shapira-Frommer, Iwona Lugowska, Tudor Ciuleanu, Miguel Quintela-Fandino, Özgür Özyılkan, Serhii Lysenko, Akira Hirasawa, Simcha Pollack, Rachel Salisbury, Alexander Gozman, Michele Maio. KEYLYNK-007: Tumor agnostic trial of olaparib plus pembrolizumab in homologous recombination repair mutation- and homologous recombination deficiency- positive advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT004.