Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
A phase 2 multicenter trial of rucaparib and nivolumab as maintenance therapy in patients with advanced biliary tract cancer: BilT-02.
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Mohan Arathi, Griffith Kent A, Goff Laura W, Crysler Oxana, Enzler Thomas, Cardin Dana B, Gunchick Valerie, Tsang Ashley P, Dippman Dominique, Young Allison S, Olivei Alberto C, Mannan Rahul, Rao Arvind, Frankel Timothy L, Kumar-Sinha Chandan, Zalupski Mark M, Sahai Vaibhav
Аннотация
PURPOSE: This phase 2 trial investigated rucaparib (PARP inhibitor) in combination with nivolumab in patients with advanced BTC without progression after 4-6 months of first-line platinum-based chemotherapy.
PATIENTS AND METHODS: The primary endpoint was 4-month progression-free survival (PFS) rate with null and alternative hypotheses of 63% and 85%. Secondary endpoints included PFS rate in patients with DNA damage repair (DDR) and IDH1 mutations, median PFS and overall survival (OS) from start of study treatment (PFS1, OS1) and first-line chemotherapy (PFS2, OS2), best overall response and safety; NCT03639935.
RESULTS: Of 31 patients, 24 (77.6%) had ECOG performance status 1 and 22 (71.0%) intrahepatic cholangiocarcinoma. Nine (29%) patients had DDR or IDH1 mutations (BRCA2 (n = 3), ATM (2), FANCA (1), IDH1 (3)). 4-month PFS rate was 54.8% (95% confidence intervals (CI), 36.0-72.7) in all patients, and 83.3% and 100% in the DDR and IDH1 cohorts, respectively. Median PFS1 and OS1 were 4.6 months (95% CI, 3.7-6.2) and 15.9 months (95% CI, 9.8-24.1). Median PFS2 and OS2 were 9.9 months (95% CI, 8.3-11.3) and 21.4 months (95% CI, 14.8-26.7). Two (6.4%) patients had partial response. Most common grade ≥ 3 TRAEs included anemia (12.9%), neutropenia (9.7%) and elevated liver enzymes (12.9%).
CONCLUSION: The primary endpoint of PFS rate at 4 months was not met. The PFS rate at 4 months in the DDR and IDH1 cohorts were longer than expected and support further investigation of the addition of PARP inhibitor during maintenance immune-checkpoint inhibition for DDR and IDH1 altered BTC patients.
PATIENTS AND METHODS: The primary endpoint was 4-month progression-free survival (PFS) rate with null and alternative hypotheses of 63% and 85%. Secondary endpoints included PFS rate in patients with DNA damage repair (DDR) and IDH1 mutations, median PFS and overall survival (OS) from start of study treatment (PFS1, OS1) and first-line chemotherapy (PFS2, OS2), best overall response and safety; NCT03639935.
RESULTS: Of 31 patients, 24 (77.6%) had ECOG performance status 1 and 22 (71.0%) intrahepatic cholangiocarcinoma. Nine (29%) patients had DDR or IDH1 mutations (BRCA2 (n = 3), ATM (2), FANCA (1), IDH1 (3)). 4-month PFS rate was 54.8% (95% confidence intervals (CI), 36.0-72.7) in all patients, and 83.3% and 100% in the DDR and IDH1 cohorts, respectively. Median PFS1 and OS1 were 4.6 months (95% CI, 3.7-6.2) and 15.9 months (95% CI, 9.8-24.1). Median PFS2 and OS2 were 9.9 months (95% CI, 8.3-11.3) and 21.4 months (95% CI, 14.8-26.7). Two (6.4%) patients had partial response. Most common grade ≥ 3 TRAEs included anemia (12.9%), neutropenia (9.7%) and elevated liver enzymes (12.9%).
CONCLUSION: The primary endpoint of PFS rate at 4 months was not met. The PFS rate at 4 months in the DDR and IDH1 cohorts were longer than expected and support further investigation of the addition of PARP inhibitor during maintenance immune-checkpoint inhibition for DDR and IDH1 altered BTC patients.