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Abstract：
BACKGROUND: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein-1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors.
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.
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.
摘要：
背景：Retifanlimab是一种针对程序性死亡蛋白1的人源化单克隆抗体，INCB001158是一种口服精氨酸酶抑制剂。本Ib期研究调查了retifanlimab，INCB001158及其在日本晚期实体瘤患者中的组合。
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。
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。
