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Hepatology. 2025;81(3):823-836.

Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

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제1저자 오도연 · 교신저자 오도연

PMID 38875119 PMC11825481 DOI 10.1097/HEP.0000000000000965 IF 18 혈액종양내과
소속 (18)
  1. Division of Medical Oncology, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
  2. Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea.
  3. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  4. Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
  5. Department Medical Oncology, Bradford Hill Centro de Investigación Clínica, Santiago, Chile.
  6. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
  7. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
  8. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
  9. Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
  10. Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  11. Department of Hematology-Oncology, Mayo Clinic, Phoenix, Arizona, USA.
  12. Department Medical Oncology, University of Milan, Fondazione IRCCS Istituto Nazionale del Tumori, Milan, Italy.
  13. Department of Oncology, University College London Cancer Institute, London, UK.
  14. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  15. Department of Gastrointestinal Oncology, Mainz University Hospital, Mainz, Germany.
  16. Global Medical Affairs Oncology, Merck Serono S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany.
  17. Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, Darmstadt, Germany.
  18. Asan Medical Center, Department of Oncology, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract

BACKGROUND AND AIMS We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer.

APPROACH AND RESULTS This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer. Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m 2 +cisplatin 25 mg/m 2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149). The primary end point was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survival events had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable]) and placebo (11.5 mo [10.0-not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66-2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively.

CONCLUSIONS BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1
FIGURE 1 Trial profile. Abbreviations: AE, adverse event; GemCis, gemcitabine+cisplatin; PD, progressive disease.
FIGURE 2
FIGURE 2 Overall survival (primary end point)—randomized double-blind phase. Abbreviations: GemCis, gemcitabine+cisplatin; NE, not estimable; OS, overall survival.
FIGURE 3
FIGURE 3 Progression-free survival according to RECIST v1.1 (as adjudicated by the IRC). Abbreviations: GemCis, gemcitabine+cisplatin; IRC, Independent Review Committee; RECIST, Response Evaluation Criteria in Solid Tumors.
FIGURE 4
FIGURE 4 Waterfall plot (A and B) and Spider plot (C and D) of percent change (from baseline) in the sum of diameters of all target lesions. Abbreviations: CR, complete response; GemCis, gemcitabine+cisplatin; IRC, Independent Review Committee; NE, not estimable; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

그림 출처: PubMed Central 공개 논문 (PMC11825481)

Conflict of interest statement

Do-Youn Oh advises and received grants from AstraZeneca, BeiGene, Merck & Co, Kenilworth, NJ, and Novartis. She advises Arcus, ASLAN, Basilea, Bayer, Bristol Myers Squibb/Celgene, Genentech/Roche, Halozyme, IQVIA, Taiho, Turning Point, Yuhan, and Zymeworks. She received grants from Array, Eli Lilly, Handok, and Servier. Masafumi Ikeda is on the speakers’ bureau and received grants from AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Merck & Co, Kenilworth, NJ, NIHON SERVIER, Novartis, Takeda, and Yakult. He is on the speakers’ bureau for AbbVie, Abbott, EA Pharma, Fujifilm Toyama Chemical, Incyte, Nippon Kayaku, Otsuka, Teijin, Taiho, and Taisho. He received grants from Chiome, Delta-Fly, Invitae, J-Pharma, Merck KGaA, Merus, Ono, Pfizer, and Syneos Health. Choong-kun Lee is on the speakers’ bureau and received grants from Boryung. He consults for Roche. He advises AstraZeneca. He is on the speakers’ bureau for Dong-A ST, Servier, and Novartis. He received grants from Celltrion and GC Biopharma. Carlos Rojas consults, advises, and is on the speakers’ bureau for Bristol Myers Squibb, Merck & Co, Kenilworth, NJ, Pfizer, and Roche. He consults and advises Tecnofarma. He is on the speakers’ bureau AstraZeneca and Knight. He advises Sanofi. Chih-Hung Hsu consults, advises, received grants from AstraZeneca. He consults, is on the speakers’ bureau, and received grants from Bristol Myers Squibb, Ono, and Roche. He advises and received grants from Merck KGaA. He is on the speakers’ bureau and received grants from Eisai and Merck & Co, Kenilworth, NJ. He consults for Daiichi Sankyo. He received grants from BeiGene, Encure, Ipsen, Johnson & Johnson, MSD, NuCana Biomed, Surface Oncology, and Taiho. Jin Won Kim consults for AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, Merck & Co, Kenilworth, NJ, Ono, Sanofi-Aventis, Servier, and TCUBEit. He received grants from HK inno.N and Jeil Pharm. Lin Shen consults for Haichuang, Herbour, and Mingji. He advises AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck & Co, Kenilworth, NJ, Merck KGaA, Roche, Sanofi, and Servier. He received grants from Beihai Kangcheng, Beijing Xiantong Biomedical, Jacobio, Qilu, Yaojie Ankang Baiji Shenzhou, and ZaiLab. Junji Furuse advises, is on the speakers’ bureau, and received grants from AstraZeneca, Chugai Pharma, Merck & Co, Kenilworth, NJ, and Taiho. He advises and received grants from Astellas, Delta-Fly-Pharma, and J-Pharma. He is on the speakers’ bureau and received grants from Daiichi Sankyo, Eisai, Incyte, Ono, and Takeda. He advises Fujifilm, Merck KGaA, Onco Therapy, and Takara Bio. He is on the speakers’ bureau for Bayer, EA Pharma, Eli Lilly, Fujifilm, MSD, Novartis, Servier, Teijin, Terumo, and Yakult. He received grants from Sanofi and Sumitomo Dainippon. Joon Oh Park consults, advises, and received grants from Servier. He consults and advises ImmuneOncia. He advises AstraZeneca, Adicet, Arcus, MediRama, and Merck KGaA. He received grants from ABL Bio, Bristol Myers Squibb, Eutilex, MedPacto, and Minneamrita. Mitesh Borad consults and advises ADC Therapeutics, Excelixis, Inspyr, G1, Genentech, Huya, Immunovative, Lynx Group, Merck & Co, Kenilworth, NJ, OncBioMune, and Western Oncolytics. He received grants from Adaptimmune, Agios, Basilea, Boston Biomed, Celgene, Dicerna, EMD Serona, Halozyme, Incyte, Isis Pharmaceuticals, Merck KGaA, Mirna, Redhill, Senhwa, Sun Biopharma, Taiho, and Toray. Filippo de Braud consults, advises, is on the speakers’ bureau, and received grants from Bristol Myers Squibb. He consults, is on the speakers’ bureau, and received grants from AstraZeneca, Merck & Co, Kenilworth, NJ, Pfizer, and Roche. He advises, is on the speakers’ bureau, and received grants from Sanofi. He consults and advises Pierre Fabre and Taiho. He consults and is on the speakers’ bureau for Bayer, Dephaforum, and Ignyta. He consults and received grants from Amgen, Celgene, Incyte, and Novartis. He consults for Daiichi Sankyo, Eli Lilly, Fondazione Menarini, Gentili, IQVIA, Indena, Mattioli 1885, MSD, Menarini, Octimet Oncology, Pharm Research Associated, Servier, and Tiziana Life Sciences. He is on the speakers’ bureau for Accmed, Ambrosetti, Biotechespert, Dynamicom Education, Effetti, ESO, Events, Fare Comunicazione, Idea-z, Itanet, Motore Sanità, Nadirex, and Prime Oncology. He received grants from Kymab, Merck KGaA, NMS, and Tesaro. John Bridgewater consults and advises Merck KGaA. He advises and is on the speakers’ bureau for Incyte and Servier. He advises Taiho. Markus Moehler is on the speakers’ bureau and received grants from Merck KGaA. Francois Audhuy is employed by Merck Serono S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. Motonobu Osada is employed by Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, Darmstadt, Germany. Masashi Sato is employed by Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, Darmstadt, Germany. Changhoon Yoo consults, advises, and received grants from AstraZeneca, Bayer, Boryung, Celgene, CKD, HK inno.N, Ildong, and Ono. He consults and advises Ipsen and Servier. He consults and received grants from Ipsen, and Servier. He consults for Bristol Myers Squibb, Debiopharm, Eisai, Janssen, Kyowa Kirin, Merck & Co, Kenilworth, NJ, Merck KGaA, Mundipharma, Novartis, and Roche. He received grants from Eisai and MSD. The remaining authors have no conflicts to report.

그 밖의 정보
출판 형태
Adaptive Clinical Trial, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
저널
Hepatology (Baltimore, Md.) · eISSN 1527-3350
전자 출판
2024-06-14
MeSH
Adult · Aged · Female · Humans · Male · Middle Aged · Antineoplastic Combined Chemotherapy Protocols* / administration & dosage / adverse effects / therapeutic use · Biliary Tract Neoplasms* / drug therapy / mortality / pathology · Cisplatin / administration & dosage / adverse effects · Deoxycytidine* / analogs & derivatives / administration & dosage / adverse effects · Double-Blind Method · Gemcitabine · Recombinant Proteins / administration & dosage / adverse effects · Treatment Outcome
Substances
Cisplatin · Deoxycytidine · Gemcitabine · Recombinant Proteins
데이터
ClinicalTrials.gov: NCT04066491
참고문헌
37편