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Abstract：
BACKGROUND: Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study.
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.
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.
摘要：
背景：程序性死亡-1（PD-1）抑制剂，包括Nivolumab,在先前接受过治疗的微卫星不稳定性高/错配修复缺陷（MSI-H/dMMR）转移性结直肠癌（CRC）患者中，已经证明了长期生存获益。PD-1和淋巴细胞活化基因3（LAG-3）是不同的免疫检查点，通常在肿瘤浸润淋巴细胞上共表达，并导致肿瘤介导的T细胞功能障碍。Relatlimab是一种LAG-3抑制剂，在黑色素瘤患者中与nivolumab联合使用已显示出疗效。这里,我们在CheckMate142研究中介绍了接受nivolumab联合relatlimab治疗的MSI-H/dMMR转移性CRC患者的结果.
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。
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。
