Background Early detection and management of treatment‐related adverse events (TRAEs) in patients receiving immune checkpoint inhibitors may improve outcomes. In CheckMate 142, nivolumab (3 mg/kg) plus low‐dose ipilimumab (1 mg/kg) provided durable clinical benefit (objective response rate ORR 55%, median duration of response not reached, 12‐month overall survival OS rate 85%) and manageable safety for previously treated microsatellite instability‐high and/or mismatch repair‐deficient (MSI‐H/dMMR) metastatic colorectal cancer (mCRC). In‐depth safety and additional efficacy outcomes from CheckMate 142 are presented. Materials and Methods Safety assessments included frequency of TRAEs, select TRAEs (sTRAEs), and immune‐mediated adverse event incidences; time to onset (TTO); time to resolution (TTR); immune‐modulating medication (IMM) use; dose delay; and sTRAE occurrence after resuming therapy. Efficacy assessments included ORR and survival analyses in patients with sTRAEs with or without concomitant IMM treatment and patients without sTRAEs. Results Among 119 patients, 25%, 23%, 19%, 5%, 5%, and 29% experienced an endocrine, gastrointestinal, hepatic, pulmonary, renal, or skin sTRAE, respectively; the majority (57%) were grade 1/2. sTRAEs occurred early (median TTO, 5.2–12.6 weeks). Nonendocrine sTRAEs resolved in most (>71%) patients (median TTR, 1.5–9.0 weeks). IMMs were used to manage sTRAEs in 22%–56% of patients (most resolved). Of patients with dose delay because of sTRAEs, 25 of 29 resumed treatment. Patients with or without sTRAEs had comparable ORR (57% vs. 52%) and 12‐month OS rates (93% vs. 75%). Similar results were observed in patients with or without sTRAEs regardless of IMM use (ORR 52% vs. 57%; OS rates 87% vs. 82%). Conclusion The benefit‐risk profile of nivolumab plus low‐dose ipilimumab provides a promising treatment option for patients with previously treated MSI‐H/dMMR mCRC. Implications for Practice Nivolumab (NIVO) plus low‐dose (1 mg/kg) ipilimumab (IPI) received U.S. Food and Drug Administration approval for patients with microsatellite instability‐high and/or mismatch repair‐deficient (MSI‐H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on results from CheckMate 142. In this safety analysis, the majority of select treatment‐related adverse events (sTRAEs) occurred early, were managed using evidence‐based treatment algorithms, and resolved. Efficacy outcomes were comparable between patients with or without sTRAEs regardless of the use of concomitant immune‐modulating medications. The benefit‐risk profile of NIVO + low‐dose IPI provides a promising treatment option for MSI‐H/dMMR mCRC. 摘要 背景。在接受免疫检查点抑制剂治疗的患者中，早期发现和管理治疗相关不良事件 (TRAE) 可改善预后。在 CheckMate 142 研究中，纳武单抗 (3 mg/kg) 联合低剂量易普利姆玛单抗 (1 mg/kg) 可提供持久的临床疗效 客观反应率 (ORR)为 55%，未达到中位反应持续时间，12 个月的总生存(OS)率为 85%，且对于既往已接受微卫星不稳定性高/错配修复缺陷(MSI‐H/dMMR)转移性结直肠癌 (mCRC) 治疗的患者具有可控的安全特性。此外，还介绍了 CheckMate 142 的深度安全性及其他疗效。 材料和方法。安全性评估包括TRAE发生频率、选择性TRAE (sTRAE) 及免疫介导型不良事件的发生率；发生时间 (TTO)；消退时间 (TTR)；免疫调节药物 (IMM) 的使用；剂量延迟；恢复治疗后出现sTRAE。疗效评估包括对sTRAE伴有或不伴IMM的患者及不伴sTRAE的患者的ORR和生存率进行分析。 结果。在 119 名患者中，25%、23%、19%、5%、5% 及 29% 的患者分别出现了内分泌系统、胃肠、肝脏、肺、肾脏或皮肤方面的sTRAE；多数 (57%) 属于 1/2 级。sTRAE发生于早期(中位TTO，5.2–12.6 周)。多数(超过 71%)患者的非内分泌系统sTRAE消退(中位TTR，1.5–9.0 周)。22%–56% 的患者使用IMM治疗sTRAE(多数均消退)。在由于sTRAE而导致剂量延迟的患者中，29 例中有 25 例恢复了治疗。对于伴有或不伴sTRAE的患者，在ORR(57% vs. 52%)和 12 个月的OS率(93% vs. 75%)方面相差无几。经观察发现，无论IMM使用与否，伴有或不伴sTRAE的患者均取得了类似的疗效(ORR 52% vs. 57%；OS率 87% vs. 82%)。 结论。根据对纳武单抗联合低剂量易普利姆玛单抗的疗效‐风险分析，此种疗法将有望成为既往已接受MSI‐H/dMMR mCRC治疗者的首选治疗方案。 实践意义:纳武单抗 (NIVO) 联合低剂量 (1 mg/kg) 易普利姆玛单抗 (IPI) 疗法获得了美国食品和药品管理局的批准，可用于患微卫星不稳定高/错配修复缺陷 (MSI‐H/dMMR) 转移性结直肠癌 (mCRC) 且在接受氟尿嘧啶、奥沙利铂及伊立替康的治疗后病情恶化(基于 CheckMate 142 研究的结果)的患者。在此项安全性分析中，大多数选择性治疗相关不良事件 (sTRAE) 均发生于早期，在采用循证治疗方法进行治疗后消退。无论是否同时使用免疫调节药物，伴有或不伴sTRAE的患者均取得了类似的疗效。根据对NIVO联合低剂量IPI的疗效‐风险分析，此种疗法将有望成为MSI‐H/dMMR mCRC的首选治疗方案 Because of unique mechanisms of action, immune checkpoint inhibitor use is associated with adverse events that differ from chemotherapy‐related adverse events. This article analyzes the safety profile of nivolumab plus low‐dose ipilimumab in previously treated patients with microsatellite instability‐high and/or mismatch repair‐deficient metastatic colorectal cancer.