Rucaparib Plus Nivolumab Shows Biomarker-Linked Activity in Advanced Biliary Tract Cancer

Results from the Phase 2 BilT-02 Trial 

Clinical Summary:

• Design/Population: BilT-02 was a multicenter, single-arm trial evaluating maintenance rucaparib plus nivolumab in patients with advanced biliary tract cancer whose disease had not progressed after 4 to 6 months of first-line platinum-based chemotherapy.
• Key Outcomes: The regimen did not meet the prespecified 4-month progression-free survival target, although stable disease was common and greater disease control was observed in patients with DNA damage response (DDR) or IDH1 alterations. Grade 3 to 5 treatment-related adverse events occurred in 54.8% of patients, including 1 treatment-related death from immune checkpoint inhibitor–related myocarditis.
• Clinical Relevance: Although these findings do not support maintenance rucaparib plus nivolumab in an unselected advanced biliary tract cancer population, the activity observed in DDR-and IDH1-altered disease supports further evaluation in biomarker-selected populations. 

Results from the phase 2 BilT-02 trial showed that maintenance rucaparib plus nivolumab did not meet the prespecified 4-month progression-free survival (PFS) target in patients with advanced biliary tract cancer, although exploratory analyses identified greater disease control among patients with DNA damage response (DDR) or IDH1 alterations. 

“Despite advances in first-line treatment, durable disease control is infrequent, especially during [immune checkpoint inhibitor] maintenance therapy,” stated Arathi Mohan, MD, University of Michigan, Ann Arbor, Michigan, and coauthors. “PARP inhibition may enhance the efficacy of immune checkpoint inhibition through increased tumor immunogenicity.”

In this multicenter, single-arm trial, 31 patients with unresectable advanced biliary tract cancer whose disease had not progressed after 4 to 6 months of first-line platinum-based chemotherapy received 600 mg of oral rucaparib twice daily plus 240 mg of intravenous nivolumab on days 1 and 15 of each 28-day cycle for up to 2 years. The primary end point was the 4-month PFS rate. Key secondary end points included PFS, overall survival (OS), objective response, and safety.

At analysis, the 4-month PFS rate was 54.8%. Median PFS from the start of maintenance therapy was 4.6 months, and median OS was 15.9 months. Among 30 response-evaluable patients, 2 achieved a partial response and 23 had stable disease.

Exploratory genomic analyses suggested greater activity in selected molecular subgroups. The 4-month PFS rate was 83.3% among 6 patients with DDR alterations involving BRCA2, ATM, or FANCA and 100% among 3 patients with IDH1 mutations. PFS durations among the 3 patients with IDH1-mutant disease were 8.5 months, 9.2 months, and 18.5 months, respectively. Given the small number of patients, these biomarker findings remain hypothesis-generating. 

Grade 3 to 5 treatment-related adverse events occurred in 54.8% of patients, with anemia and neutropenia among the most common severe toxicities. One treatment-related death from immune checkpoint inhibitor–related myocarditis was reported.

“This supports further clinical investigation of the addition of a PARP inhibitor during maintenance [immune checkpoint inhibitor] monotherapy for the DDR and IDH1-altered patients with this rare cancer,” concluded Dr Mohan et al. 

Source:

Mohan A, Griffith KA, Goff LW, et al. A phase II multicenter trial of rucaparib and nivolumab as maintenance therapy in patients with advanced biliary tract cancer: BilT-02. Clin Cancer Res. Published online: August 7, 2026 doi: 10.1158/1078-0432.ccr-25-1114