A randomized phase 2 trial of nivolumab, gemcitabine, and cisplatin or nivolumab and ipilimumab in previously untreated advanced biliary cancer: BilT-01

Abstract

Background: Gemcitabine and cisplatin has limited benefit as treatment for advanced biliary tract cancer (BTC). The addition of an anti-programmed death receptor (PD-1)/PD-ligand (L1) antibody to either systemic chemotherapy or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibody has shown benefit in multiple solid tumors.

Methods: In this phase 2 trial, patients 18 years or older with advanced BTC without prior systemic therapy and Eastern Cooperative Oncology Group Performance Status 0-1 were randomized across six academic centers. Patients in Arm A received nivolumab (360 mg) on day 1 along with gemcitabine and cisplatin on days 1 and 8 every 3 weeks for 6 months followed by nivolumab (240 mg) every 2 weeks. Patients in Arm B received nivolumab (240 mg) every 2 weeks and ipilimumab (1 mg/kg) every 6 weeks.

Results: Of 75 randomized patients, 68 received therapy (Arm A = 35, Arm B = 33); 51.5% women with a median age of 62.5 years. The observed primary outcome of 6-month progression-free survival (PFS) rates in the evaluable population was 59.4% in Arm A and 21.2% in Arm B. The median PFS and overall survival (OS) in Arm A were 6.6 and 10.6 months, and in Arm B 3.9 and 8.2 months, respectively, in patients who received any treatment. The most common treatment-related grade 3 or higher hematologic adverse event was neutropenia in 34.3% (Arm A) and nonhematologic adverse events were fatigue (8.6% Arm A) and elevated transaminases (9.1% Arm B).

Conclusions: The addition of nivolumab to chemotherapy or ipilimumab did not improve 6-month PFS. Although median OS was less than 12 months in both arms, the high OS rate at 2 years in Arm A suggests benefit in a small cohort of patients.

Trial registration: ClinicalTrials.gov NCT03101566.

Keywords: chemo immunotherapybiliary cancer; cholangiocarcinoma; immune checkpoint blockade; immunotherapy.

Conflict of interest statement

Vaibhav Sahai reports institutional grant funding from Agios, Bristol‐Myers Squibb, Celgene, Clovis, Exelixis, Fibrogen, Incyte, Ipsen, Medimmune, Merck, and Rafael; and consultant fees from AstraZeneca, GlaxoSmithKline, Histosonics, Incyte, QED and Rafael. Kent A. Griffith reports institutional grant funding from Bristol‐Myers Squibb, AstraZeneca, Merch Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, and Tolero Pharmaceuticals; and consultant fees from Ipsen, Array BioPharm, AstraZeneca, Cancer Commons, Legend Biotech, and Foundation Medicine. Walid L. Shaib reports institutional grant funding from GlaxoSmithKline, Lexicon, Tesaro, Eli Lilly; and consultant fees from Ipsen, Lexicon, Mylan, Bristol‐Myers Squibb, and BluePrint Therapeutics. Devalingam Mahalingam reports institutional grant funding from Amgen, Merck, and Oncolytics; and consultant fees from Qurient, Oncoone, Bristol‐Myers Squibb, Eisai and Exelixis. David B. Zhen reports institutional grant funding from Merck, SeaGen, Daiichi‐Sankyo, and AstraZeneca. Dustin A. Deming reports institutional grant funding from Merck, Arcus, Bristol‐Myers Squibb, Aadi, Takeda, and AstraZeneca; and advisory board member for Eli Lilly, Seattle Genetics, Bayer, and Promega. Mark M. Zalupski reports institutional grant funding from AstraZeneca, MedImmune and Seattle Genetics. The other author made no disclosures.

© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Figures

FIGURE 1

Patient disposition.

FIGURE 2

Kaplan–Meier analyses of (A) progression‐free survival and (B) overall survival.