A Phase II Multicenter Trial of Rucaparib and Nivolumab as Maintenance Therapy in Patients with Advanced Biliary Tract Cancer: BilT-02

This phase II trial investigated rucaparib [poly (ADP-ribose) polymerase (PARP) inhibitor] in combination with nivolumab in patients with advanced biliary tract cancer (BTC) without progression after 4 to 6 months of first-line platinum-based chemotherapy.

The primary endpoint was the 4-month progression-free survival (PFS) rate with null and alternative hypotheses of 63% and 85%. Secondary endpoints included the PFS rate in patients with DNA damage response (DDR) and isocitrate dehydrogenase 1 (IDH1) mutations, median PFS and overall survival (OS) from the start of study treatment (PFS1 and OS1) and first-line chemotherapy (PFS2 and OS2), best overall response, and safety (NCT03639935).

Of 31 patients, 24 (77.6%) had Eastern Cooperative Oncology Group performance status 1, and 22 (71%) had intrahepatic cholangiocarcinoma. Nine (29%) patients had DDR or IDH1 mutations [BRCA2 (n = 3), ATM (2), FANCA (1), and IDH1 (3)]. Four-month PFS rate was 54.8% [95% confidence intervals (CI), 36-72.7] 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), respectively. Median PFS2 and OS2 were 9.9 months (95% CI, 8.3-11.3) and 21.4 months (95% CI, 14.8-26.7), respectively. Two (6.4%) patients had a partial response. The most common grade ≥3 treatment-related adverse events included anemia (12.9%), neutropenia (9.7%), and elevated liver enzymes (12.9%).