Rolfo Christian, Greillier Laurent, Veillon Remi, Badin Firas, Ghiringhelli Francois, Isambert Nicolas, Paulus Astrid, Chaudhary Surendra Pal, Vugmeyster Yulia, Sato Masashi, Hiret Sandrine
Center for Thoracic Oncology, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.
Present affiliation: Arthur G. James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
JTO Clin Res Rep. 2024 Oct 19;6(1):100748. doi: 10.1016/j.jtocrr.2024.100748. eCollection 2025 Jan.
In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status.
In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts. Patients with previously untreated metastatic NSCLC (cohorts A, B, and C) received bintrafusp alfa with chemotherapy as first-line treatment, whereas patients whose disease progressed on previous treatment with programmed cell death protein 1 or PD-L1 inhibitors (cohort D) received bintrafusp alfa with chemotherapy as second-line treatment. The primary objective of this study was to evaluate the safety and tolerability of bintrafusp alfa with chemotherapy.
Four serious and one nonserious treatment-emergent adverse events were considered dose-limiting toxicities, none of which were assessed as related to bintrafusp alfa by the investigator. Any-grade bintrafusp alfa-related adverse events occurred in 20.7% of patients in cohorts A+B+C and in 16.7% of patients in cohort D. Keratoacanthoma was the most common transforming growth factor-β inhibition-mediated skin lesion (cohorts A+B+C: 12.1% and cohort D: 8.3%). In cohorts A+B+C, the overall response rate was 48.3%, and in patients with PD-L1 tumor proportion score of more than or equal to 50.0%, it was 71.4%. On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned.
Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC.
在一项1期研究中，发现双特异性抗体bintrafusp alfa在先前接受过治疗的晚期非小细胞肺癌（NSCLC）患者中具有令人鼓舞的临床活性。本研究评估了bintrafusp alfa联合化疗在IV期NSCLC患者中的安全性和疗效，无论其程序性死亡配体1（PD-L1）表达状态如何。
在这项开放标签的1b/2期研究（NCT03840915）中，符合条件的患者被分配到四个队列之一。先前未接受过治疗的转移性NSCLC患者（队列A、B和C）接受bintrafusp alfa联合化疗作为一线治疗，而先前接受程序性细胞死亡蛋白1或PD-L1抑制剂治疗后疾病进展的患者（队列D）接受bintrafusp alfa联合化疗作为二线治疗。本研究的主要目的是评估bintrafusp alfa联合化疗的安全性和耐受性。
4例严重和1例非严重的治疗中出现的不良事件被认为是剂量限制性毒性，研究者均未评估其与bintrafusp alfa相关。A+B+C队列中20.7%的患者以及D队列中16.7%的患者发生了任何级别的bintrafusp alfa相关不良事件。角化棘皮瘤是最常见的转化生长因子-β抑制介导的皮肤病变（A+B+C队列：12.1%，D队列：8.3%）。在A+B+C队列中，总体缓解率为48.3%，在PD-L1肿瘤比例评分大于或等于50.0%的患者中，缓解率为71.4%。基于中期分析，数据被认为已成熟，未计划进一步分析。
发现bintrafusp alfa联合化疗在IV期NSCLC患者中具有可控的安全性和令人鼓舞的临床活性。
