The multicenter, single-arm, phase 1b/2 BilT-03 study evaluated the benefit of a chemoimmunotherapy regimen that combines the 3-drug chemotherapy regimen of liposomal irinotecan, 5-fluorouracil (5-FU), and leucovorin, plus the PD-1 monoclonal antibody nivolumab, as second-line therapy in patients with advanced biliary tract cancers. The results were presented by Vaibhav Sahai, MBBS, MS, University of Michigan, Ann Arbor, at the 2022 ASCO GI Cancers Symposium.
Key eligibility criteria for study enrollment included histologically confirmed unresectable or metastatic biliary tract cancer after disease progression or intolerance of first-line systemic therapy, measurable disease, ECOG performance status 0-1, and absence of autoimmune disease or chronic steroid use.
At dose level 0, the patients received the combination of 5-FU 2400 mg/m2 over 46 hours, leucovorin 400 mg/m2, liposomal irinotecan 70 mg/m2 plus the immunotherapy nivolumab 240 mg every 2 weeks, for up to 2 years, until disease progression or unacceptable adverse events.
The phase 1b portion of the study included 10 patients and its primary objective was to determine the recommended phase 2 dose, based on the probability of dose-limiting toxicity rate of <30% in days 1 to 29. The primary end point of the phase 2 portion of the study was the median progression-free survival (PFS) rate. The threshold for alternative hypothesis was 5 months, and the null hypothesis was 2.9 months (2-sided alpha 0.05, power 80%).
Secondary end points included best overall response rate (ORR), PFS, overall survival (OS), and safety. Exploratory objectives included biomarker analysis using a targeted panel of exome and transcriptome, and immune-cell subsets. Patients were enrolled in 4 sites in the United States between June 2019 and July 2021.
A total of 30 patients were included in the study—10 patients in phase 1b and 20 patients in the phase 2 portion of the study. The median age of the total study population was 63.5 years (range, 36-75 years); the majority (60%) were men, 57% had ECOG performance status 1, 70% had metastatic disease, and 63% had intrahepatic cholangiocarcinoma (CCA).
In phase 1b, 1 patient had a dose-limiting grade 3 adverse event (enterocolitis) at dose level 0; the recommended phase 2 dose was confirmed at dose level 0. The median PFS was 5.37 months, which met the primary end point versus a historical PFS of 2.9 months (null hypothesis).
At a median follow-up of 11.5 months, the median OS was 7.8 months (95% confidence interval, 5.8-21.4). The ORR was 10%, including 3 partial responses, and the disease control rate was 53%. The most common nonhematologic adverse events of any grade were diarrhea (60%), nausea (46.7%), fatigue (43.3%), and vomiting (26.7%).
Based on results of the BilT-03 study, the investigators concluded that the combination chemoimmunotherapy regimen of liposomal-irinotecan, 5-FU, and leucovorin plus nivolumab may be of benefit to a subset of patients with advanced biliary tract cancer, including patients with intrahepatic CCA.
Sahai V, Griffith KA, Lin BSL, et al. A multicenter phase Ib/II study of liposomal-irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) with nivolumab as second-line therapy for patients with advanced biliary tract cancer (BilT-03). Abstract 438.
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