A multicenter randomized phase II study of nivolumab in combination with gemcitabine/cisplatin or ipilimumab as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-01).

Abstract

4582 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis with a median overall survival (OS) less than 12 months (mos). This randomized phase 2, multi-institutional, study was designed to investigate the role of combinational immunotherapy, using nivolumab (nivo) with gemcitabine (gem)/cisplatin (cis), or nivo with ipilimumab (ipi) in pts with untreated advanced BTC. Methods: Key eligibility criteria include histologically confirmed unresectable or metastatic BTC without prior systemic therapy, measurable disease per RECISTv1.1, ECOG PS 0-1, and absence of autoimmune disease or chronic steroid use. Arm A included gem 1000 mg/m2 and cis 25 mg/m2 d1, 8 Q3w + nivo 360 mg d1 Q3w for 6 mos followed by nivo 240 mg Q2w monotherapy for a total duration of 2 yrs; Arm B included nivo 240 mg Q2w and ipi 1 mg/kg Q6w for 2 yrs, in absence of disease progression. Primary endpoint is progression-free survival (PFS) rate at 6 mos with an alternative hypothesis of 80% (null hypothesis of 59%, one-sided alpha 0.05, power 80%) for each non-comparative arm. Secondary endpoints include overall response rate (ORR) per immune related (ir)RECIST, median PFS and OS and safety. Exploratory objectives include biomarker analysis using include sequential whole exome/transcriptome and immune cell subsets in tissue and blood. Results: 71 eligible pts (49% male, 83% Caucasian) with 35 in Arm and 36 in Arm B with a median age of 62 (range 20-80) yrs, and majority with metastatic disease (90%) were enrolled across 6 US sites. PFS rate at 6 mos was 70% in Arm A and 18.6% in Arm B. The median PFS was 8.8 mos (95% CI, 6.1 to 11.3) in Arm A and 4.1 mos (95% CI, 2.4-5.2) in Arm B. Ten patients on Arm A and 2 on Arm B remain on active treatment; additional 7 are in follow-up for OS. ORR, safety data and median OS evaluation are underway and will be presented at the meeting. Exploratory analyses are pending. Conclusions: The observed PFS rates at 6 mos in either arm are insufficient to reject the null hypothesis of 59% PFS at 6 months. While Arm B is inferior, Arm A appears to be as effective as standard of care although OS estimates are pending maturity. Clinical trial information: NCT03101566 .