BilT03: Phase 1b/2 multicenter trial of nivolumab with 5-fluorouracil and liposomal irinotecan for previously treated advanced biliary tract cancer.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-12-13 DOI:10.1016/j.medj.2024.10.024

Vaibhav Sahai, Kent A Griffith, Bruce S Lin, Heloisa P Soares, Sreenivasa R Chandana, Oxana Crysler, Chandan Kumar-Sinha, Thomas Enzler, Dominique Dippman, Valerie Gunchick, Mark M Zalupski

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引用次数: 0

Abstract

Background: Second-line chemotherapy with 5-fluorouracil/leucovorin (5FULV) and liposomal irinotecan improves survival in advanced biliary tract cancer (BTC). In this phase 1b/2 trial, we investigated the combination of 5FULV and liposomal irinotecan with nivolumab following progression on first-line chemotherapy for advanced BTC.

Methods: Patients received 2,400 mg/m² 5-fluorouracil, leucovorin (dose level: 0:400 or -1:200 mg/m²), 70 mg/m² liposomal irinotecan, and 240 mg nivolumab every 2 weeks (ClinicalTrials.gov: NCT03785873). The phase 1b and 2 primary objectives included recommended phase 2 dose (RP2D) and median progression-free survival (PFS; null and alternative hypotheses of 2.9 and 5.0 months) with a two-sided alpha of 0.05 and >80% power. Secondary objectives were safety, objective response rate (ORR), and overall survival (OS).

Findings: Of 30 patients with a median age of 63.5 years, 18 (60%) were men, 25 (83%) were White, 16 (53%) had an ECOG performance status of 0, and 19 (63.3%) had intrahepatic cholangiocarcinoma. In phase 1b, the RP2D was dose level 0 after a dose-limiting toxicity event of enterocolitis (n = 1). Median PFS was 4.1 months (95% confidence interval [CI], 1.9-9.9). The ORR was 16.7% (5 partial responses) per irRECIST, the median OS was 7.4 months (95% CI, 5.7-15.9), and the 24-month survival rate was 23.3%. The most common grade ≥3 treatment-related adverse events were diarrhea (5; 16.7%), fatigue (4; 13.3%), and neutropenia (3; 10%).

Conclusions: Treatment was well tolerated, but the primary endpoint was not met. The median OS was similar to prior trials with this drug combination, but the 24-month survival rate was higher than expected.

Funding: This work was funded by Ipsen Biopharmaceuticals, Bristol-Myers Squibb (CA209-8LF), and the University of Michigan Rogel Cancer Center (P30CA046592).

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.