Background

The open-label phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma. Three cohorts included patients with predominantly clear cell histology, non–clear cell histologies, or brain metastases. We report safety and efficacy from the advanced non–clear cell RCC (nccRCC) cohort of CheckMate 374.

Methods

Eligible patients received 0 to 3 prior systemic therapies. Patients received nivolumab 240 mg Q2W for ≤24 months or until confirmed progression or unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

Forty-four patients had advanced nccRCC (papillary [n = 24], chromophobe [n = 7], unclassified [n = 8], other [n = 5]); 34.1% received ≥1 prior systemic regimen in the advanced/metastatic setting. With median follow-up of 11 (range, 0.4-27) months, no all-cause grade 3-5 IMAEs or treatment-related grade 5 adverse events were reported. ORR was 13.6% (95% confidence interval [CI], 5.2-27.4), with 1 complete response (chromophobe) and 5 partial responses (papillary [n = 2], chromophobe [n = 1], collecting duct [n = 1], and unclassified [n = 1] histology). Median PFS was 2.2 months (95% CI, 1.8-5.4). Median OS was 16.3 months (95% CI, 9.2-not estimable).

Conclusions

Safety of flat-dose nivolumab 240 mg Q2W was consistent with previous results. Clinically meaningful efficacy was observed with responses in several histologies, supporting nivolumab as a treatment option for patients with advanced nccRCC, a patient population with high unmet need.

中文翻译：

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Nivolumab 在晚期非透明细胞肾细胞癌患者中的安全性和有效性：IIIb/IV 期 CheckMate 374 研究的结果。

背景

开放标签 IIIb/IV 期 CheckMate 374 研究 (NCT02596035) 旨在验证平剂量 nivolumab 240 mg 每 2 周 (Q2W) 在先前治疗的晚期/转移性肾细胞癌中的安全性和有效性。三个队列包括以透明细胞组织学、非透明细胞组织学或脑转移为主的患者。我们报告了 CheckMate 374 的高级非透明细胞 RCC (nccRCC) 队列的安全性和有效性。

方法

符合条件的患者接受了 0 到 3 次先前的全身治疗。患者接受 nivolumab 240 mg Q2W ≤24 个月或直至确认进展或出现不可接受的毒性。主要终点是高级别（3-5 级）免疫介导不良事件（IMAE）的发生率。探索性终点包括客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。

结果

44 名患者患有晚期 nccRCC（乳头状 [n = 24]、嫌色 [n = 7]、未分类 [n = 8]、其他 [n = 5]）；34.1% 的患者在晚期/转移性环境中接受了 ≥1 种先前的全身性治疗方案。中位随访 11 个月（范围 0.4-27）个月，未报告全因 3-5 级 IMAE 或治疗相关的 5 级不良事件。ORR 为 13.6%（95% 置信区间 [CI]，5.2-27.4），1 个完全缓解（嫌色）和 5 个部分缓解（乳头状 [n = 2]、嫌色 [n = 1]、集合管 [n = 1] ] 和未分类的 [n = 1] 组织学）。中位 PFS 为 2.2 个月（95% CI，1.8-5.4）。中位 OS 为 16.3 个月（95% CI，9.2-不可估计）。

结论

平剂量 nivolumab 240 mg Q2W 的安全性与之前的结果一致。在几种组织学中观察到具有临床意义的疗效，支持纳武单抗作为晚期 nccRCC 患者的治疗选择，这是一个高度未满足的患者群体。