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 : 2025-04-11 Epub Date: 2024-12-18 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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BilT03：nivolumab联合5-氟尿嘧啶和脂质体伊立替康治疗既往接受过治疗的晚期胆道癌的1b/2期多中心试验。

背景：5-氟尿嘧啶/亚叶酸素（5FULV）和伊立替康脂质体的二线化疗可提高晚期胆道癌（BTC）的生存率。在这项1b/2期试验中，我们研究了在一线化疗进展后，5FULV和伊立替康脂质体联合纳武单抗治疗晚期BTC。方法：患者每2周接受5-氟尿嘧啶2400mg /m2、亚叶酸钙（剂量水平：0:400或-1:20 0mg /m2）、伊立替康脂质体70mg /m2和纳武单抗240mg的治疗（ClinicalTrials.gov: NCT03785873）。1b期和2期的主要目标包括推荐的2期剂量（RP2D）和中位无进展生存期（PFS）；零假设和备选假设分别为2.9个月和5.0个月)，双侧α值为0.05，功率为>80%。次要目标是安全性、客观缓解率（ORR）和总生存期（OS）。结果：30例患者中位年龄为63.5岁，18例（60%）为男性，25例（83%）为White， 16例（53%）ECOG表现状态为0,19例（63.3%）为肝内胆管癌。在1b期，在肠结肠炎的剂量限制性毒性事件发生后，RP2D的剂量水平为0 （n = 1）。中位PFS为4.1个月（95%置信区间[CI]， 1.9-9.9）。每次irRECIST的ORR为16.7%（5个部分缓解），中位OS为7.4个月（95% CI, 5.7-15.9）， 24个月生存率为23.3%。最常见的≥3级治疗相关不良事件是腹泻(5；16.7%)，疲劳(4；13.3%)，中性粒细胞减少症(3；10%)。结论：治疗耐受性良好，但未达到主要终点。中位OS与先前的联合用药试验相似，但24个月生存率高于预期。资助：本研究由Ipsen Biopharmaceuticals， Bristol-Myers Squibb （CA209-8LF）和密歇根大学Rogel癌症中心（P30CA046592）资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

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