OBJECTIVES Efficacy and safety of necitumumab when combined with pembrolizumab was assessed in patients with Stage IV non-small cell lung cancer (NSCLC) of squamous and nonsquamous histology, who had progressed after treatment with a platinum-based doublet. MATERIALS AND METHODS This single-arm, multicenter, phase Ib study had a dose-finding phase, in which escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W, and expansion cohorts. Patients were treated until progressive disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent. Efficacy was evaluated by overall response rate (ORR). RESULTS In 64 treated patients (32 patients [50 %] were programmed death-ligand 1 [PD-L1] negative), confirmed ORR was 23.4 % (95 % confidence interval [CI] 13.8 %-35.7 %). Two patients (3.1 %) had complete response (CR), 13 patients (20.3 %) had partial response (PR), 26 patients (40.6 %) had stable disease, 17 patients (26.6 %) had PD, and 6 patients (9.4 %) were not evaluable. Regardless of histology or PD-L1 status, median PFS (mPFS) was 4.1 months (95 % CI 2.4-6.9 months) and OS at 6 months was 74.7 % (61.5%-83.9%). Confirmed disease control rate was 64.1 % (95 % CI 51.5-75.7). Patients with programmed death-ligand 1 (PD-L1) ≥1% had numerically improved ORR and median progression-free survival when compared with patients with PD-L1 negative cancer. No dose-limiting toxicities were recorded and the combination of necitumumab 800 mg with pembrolizumab 200 mg was considered tolerable. CONCLUSION Results suggest modest benefits of second-line necitumumab and pembrolizumab combination therapy in patients with Stage IV NSCLC. Safety profiles were consistent with class effects typical of epidermal growth factor receptor inhibitors and immunotherapies with no additive toxicities.

中文翻译：

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Necitumumab和Pembrolizumab联合治疗对IV期非小细胞肺癌患者的疗效和安全性。

目的对铂类双线药物治疗后进展的鳞状和非鳞状组织学IV期非小细胞肺癌（NSCLC）患者，评估尼妥单抗与派姆单抗联合使用时的疗效和安全性。材料与方法这项单臂，多中心，Ib期研究具有剂量确定阶段，在该阶段中，每3周（Q3W）在第1天和第8天联合给予递增剂量的尼珠单抗（600 mg和800 mg IV）， pembrolizumab（200 mg静脉注射）在第3季度的第1天，以及扩展群组。对患者进行治疗，直到进行性疾病（PD），需要停止的毒性，方案不依从或撤回同意为止。通过总反应率（ORR）评估疗效。结果在64位患者中（32位患者[50％]被编程为死亡配体1 [PD-L1]阴性），确认的ORR为23.4％（95％置信区间[CI] 13.8％-35.7％）。完全缓解（CR）的2例患者（3.1％），部分缓解（PR）的患者13例（20.3％），疾病稳定的患者26例（40.6％），PD的患者17例（26.6％），以及6例（9.4％） ％）无法评估。不论组织学或PD-L1状态如何，中位PFS（mPFS）为4.1个月（95％CI为2.4-6.9个月），而6个月时的OS为74.7％（61.5％-83.9％）。确认的疾病控制率为64.1％（95％CI 51.5-75.7）。与PD-L1阴性癌症患者相比，编程的死亡配体1（PD-L1）≥1％的患者在数字上改善了ORR和中位无进展生存期。没有剂量限制的毒性记录，认为奈妥单抗800 mg和派姆单抗200 mg的组合是可以耐受的。结论结果提示二线尼西单抗和派姆单抗联合治疗对IV期NSCLC患者有一定的益处。安全性与表皮生长因子受体抑制剂的典型类别效应和无附加毒性的免疫疗法一致。