A phase 2 multicenter trial of rucaparib and nivolumab as maintenance therapy in patients with advanced biliary tract cancer: BilT-02.

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. 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. 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%). 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.