METHODS: In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC received nivolumab 240 mg plus relatlimab 160 mg intravenously every 2 weeks. The primary end point was investigator-assessed objective response rate (ORR).
RESULTS: A total of 50 previously treated patients received nivolumab plus relatlimab. With median follow-up of 47.4 (range 43.9-49.2) months, investigator-assessed ORR was 50% (95% CI 36% to 65%) and disease control rate was 70% (95% CI 55% to 82%). The median time to response per investigator was 2.8 (range 1.3-33.1) months, and median duration of response was 42.7 (range 2.8-47.0+) months. The median progression-free survival per investigator was 27.5 (95% CI 5.3 to 43.7) months with a progression-free survival rate at 3 years of 38%, and median overall survival was not reached (95% CI 17.2 months to not estimable), with a 56% overall survival rate at 3 years. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (24%), asthenia (16%), and hypothyroidism (12%). Grade 3 or 4 TRAEs were reported in 14% of patients, and TRAEs of any grade leading to discontinuation were observed in 8% of patients. No treatment-related deaths were reported.
CONCLUSIONS: Nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR metastatic CRC.
BACKGROUND: NCT02060188.
方法:在此开放标签中,第二阶段研究,曾接受过治疗的MSI-H/dMMR转移性CRC患者每2周接受一次nivolumab240mg+relatlimab160mg静脉注射.主要终点是研究者评估的客观缓解率(ORR)。
结果:共有50例以前接受过治疗的患者接受了nivolumab联合relatlimab治疗。中位随访时间为47.4个月(范围43.9-49.2个月),研究者评估的ORR为50%(95%CI36%~65%),疾病控制率为70%(95%CI55%~82%).每位研究者的中位反应时间为2.8个月(范围1.3-33.1),中位缓解持续时间为42.7个月(范围2.8-47.0+).每位研究者的中位无进展生存期为27.5个月(95%CI5.3至43.7),3年无进展生存率为38%,未达到中位总生存期(95%CI17.2个月,不可估计),3年总生存率为56%。最常见的任何级别治疗相关不良事件(TRAEs)是腹泻(24%),虚弱(16%),和甲状腺功能减退(12%)。14%的患者报告了3级或4级TRAE,在8%的患者中观察到导致停药的任何级别的TRAEs.没有治疗相关的死亡报告。
结论:Nivolumab联合relatlimab提供了持久的临床获益,并且在先前治疗过的MSI-H/dMMR转移性CRC患者中具有良好的耐受性。
背景:NCT02060188。