A phase II single-arm study of combination pembrolizumab and olaparib in the treatment of patients with advanced biliary tract cancer

• Published in: NPJ precision oncology Vol. 9; no. 1; pp. 229 - 6
• Main Authors: Sadagopan, Narayanan, Wang, Hongkun, Yin, Chao, Weinberg, Benjamin Adam, Noel, Marcus Smith, Mukherji, Reetu, Geng, Xue, Marshall, John Lindsay, He, Aiwu Ruth
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4017; 692/4028/67/1059; 692/4028/67/1504; Anemia; Biopsy; Cancer Research; Cancer therapies; Cholangiocarcinoma; Diarrhea; Drug dosages; Gallbladder; Gene Therapy; Human Genetics; Immunotherapy; Internal Medicine; Kinases; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; Mutation; Oncology; Ovarian cancer; Patients; Radiation; Tumors
• ISSN: 2397-768X; 2397-768X
• DOI: 10.1038/s41698-025-01009-1

Effective second-line treatment for advanced biliary tract cancer (BTC) remains an unmet need. BTC often presents with homologous recombination repair (HRR) pathway deficiencies and IDH1/IDH2 mutations which suggest responsiveness to Poly (ADP-ribose) polymerase inhibitors. Thirteen patients were enrolled in our open-label, single-site phase II study of pembrolizumab and olaparib in the second-line setting and beyond for patients with advanced BTC. The objective response rate was 15.4% and the disease control rate was 53.8%. The median progression-free survival (PFS) was 5.45 months (95% CI 1.25-7.82), and the median overall survival was 7.21 months (95% CI 4.5-13.8). Both patients with IDH1 mutations and 2 of the 4 patients with HRR mutations achieved a PFS of at least 7.5 months. All BTC patients do not appear to benefit from pembrolizumab plus olaparib, but those with HRR deficiencies and/or IDH mutations may benefit although it would now represent a rechallenge with immunotherapy. Trial registration: NCT04306367, date of registration 3/10/2020.