Multicenter phase 2 trial of rucaparib and nivolumab maintenance therapy in advanced biliary tract cancer

The multicenter phase 2 BilT-02 trial in the United States investigated the combination of rucaparib and nivolumab as maintenance therapy in patients with advanced biliary tract cancer (aBTC) 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%. Among 31 patients, 4-month PFS rate was 54.8% (95% CI 36-72.7), missing the primary endpoint. Among 9 patients with DNA damage response (DDR) or isocitrate dehyodrogenase 1 (IDH1) mutations, 4-month PFS rate was 83.3% and 100%, respectively. Median progression-free survival and overall survival were 4.6 months (95% CI 3.7-6.2) and 15.9 months (9.8-24.1), respectively, from start of maintenance therapy and 9.9 months (8.3-11.3) and 21.4 months (14.8-26.7), respectively, from start of first-line chemotherapy. The most common grade ≥ 3 treatment-related adverse events were anemia (12.9%), neutropenia (9.7%), and elevated liver enzymes (12.9%). The authors conclude that the primary endpoint of the PFS rate at 4 months was not met. The 4-month PFS rate in the DDR- and IDH1-mutated cohort was higher than expected and warrants further investigation.