한빛사논문
- 조회50
Lim, Ho Yeong1; Heo, Jeong2; Peguero, Julio A.3; Ryoo, Baek-Yeol4; Decaens, Thomas5; Barlesi, Fabrice6; Moehler, Markus H.7; Jehl, Genevieve8; Eggleton, S. Peter9; Bajars, Marcis10; Gulley, James L.11
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Busan, Republic of Korea
3Oncology Consultants, Houston, TX, USA
4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
5Univ. Grenoble Alpes/Hepato-Gastroenterology and Digestive Oncology department, CHU Grenoble Alpes/Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France
6Paris-Saclay University, Gustave Roussy Cancer Campus, Villejuif, France
7Johannes Gutenberg-University Clinic, Mainz, Germany, Mainz, Germany
8The healthcare business of Merck KGaA, Darmstadt, Germany
9Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA, Darmstadt, Germany
10The healthcare business of Merck KGaA, Darmstadt, Germany
11Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Correspondence : James L. Gulley
Abstract
Background and aims: Simultaneous inhibition of the TGF-β and PD-L1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking PD-L1, was evaluated in patients with advanced HCC.
Approach and results: In this global, open-label, phase 1 study (NCT02517398), patients with PD-L1-unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200 mg every 2 weeks in a dose-escalation (n=38) or dose-expansion (n=68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal. Primary endpoint was best overall response (BOR) per Response Evaluation Criteria in Solid Tumors 1.1 by independent review committee. Secondary endpoints included investigator-assessed BOR, safety, and pharmacokinetics. Median follow-up times (range) were 41.4 (39.8-44.2) and 38.6 (33.5-39.7) months in the dose-escalation and dose-expansion cohorts, respectively. The objective response rate (ORR) was below the prespecified 20% ORR threshold set to evaluate efficacy of bintrafusp alfa in both cohorts (10.5% and 8.8%, respectively). Median overall survival and progression-free survival, respectively, were 13.8 and 1.5 months in the dose-escalation cohort and 13.5 and 1.4 months in the dose-expansion cohort. Treatment-related adverse events occurred in 78.9% and 64.7% of patients in the respective cohorts (grade ≥3 in 18.4% and 25.0% of patients).
Conclusions: Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-29)
- 국내+국외 연구진
- 의약학 > 종양의학
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