METHODS: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2. Primary endpoints were safety, tolerability, dose-limiting toxicities (DLTs), and determination of recommended phase II doses in Japanese patients.
RESULTS: Eighteen patients (retifanlimab or INCB001158 monotherapy and combination; n = 6 each) were enrolled at 2 sites in Japan. There were no DLTs, fatal adverse events (AEs), or discontinuations due to AEs. Rash (all grade 1) was the most common treatment-emergent AE with retifanlimab (n = 6). Treatment-related AEs were reported with retifanlimab (n = 4) or INCB001158 (n = 2) monotherapy and with combination (n = 4); an immune-related AE (thyroid disorder, grade 2) was reported with combination. Two responses were observed with retifanlimab monotherapy (1 complete, 1 partial) and 1 stable disease (SD), for an overall response rate of 33.3% (95% confidence interval [CI], 4.3-77.7) and disease control rate (DCR) of 50% (95% CI, 11.8-88.2). Three patients had SD with INCB001158 monotherapy (DCR 50%; 95% CI, 11.8-88.2). No responses or SD were observed with combination therapy.
CONCLUSIONS: Retifanlimab, INCB001158, and their combination had acceptable safety profiles. Promising retifanlimab antitumor activity warrants further investigation in Japanese patients.
方法:患者在第1部分中接受了retifanlimab(每4周500mg[Q4W]静脉注射)或递增剂量的INCB001158(75或100mg,每天两次[BID])单药治疗,在第2部分中接受了retifanlimab(500mgQ4W)和INCB001158(100mgBID)的主要终点是安全性,耐受性,剂量限制毒性(DLT),并确定日本患者的推荐II期剂量。
结果:18例患者(retifanlimab或INCB001158单药和联合治疗;n=6)在日本的2个地点登记。没有DLT,致命不良事件(AE),或因不良事件而停产。皮疹(均为1级)是retifanlimab最常见的治疗引起的AE(n=6)。retifanlimab(n=4)或INCB001158(n=2)单药治疗和联合治疗(n=4)报告了治疗相关的AE;免疫相关的AE(甲状腺疾病,2级)结合报告。用retifanlimab单药治疗观察到两个反应(1个完全,1个部分)和1个稳定的疾病(SD),总有效率为33.3%(95%置信区间[CI],4.3-77.7)和疾病控制率(DCR)为50%(95%CI,11.8-88.2)。三名患者使用INCB001158单药治疗(DCR50%;95%CI,11.8-88.2)。联合治疗未观察到反应或SD。
结论:Retifanlimab,INCB001158及其组合具有可接受的安全性。有希望的retifanlimab抗肿瘤活性值得在日本患者中进行进一步研究。