抗细胞毒性 T 淋巴细胞相关抗原 4 单克隆抗体 quavonlimab 联合 pembrolizumab 治疗既往治疗的广泛期小细胞肺癌的安全性和疗效：一项 I 期研究结果。
Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer.
机构信息
Yonsei Cancer Center, 50-1 Yonsei-ro Sinchon-dong, Seodaemun-gu, Seoul, South Korea; Yonsei University College of Medicine, 107-11 Sinchon-dong, Seodaemun-gu, Seoul, South Korea.
National Cancer Center Hospital East, 6 Chome Kashiwanoha, Kashiwa, Chiba 277-0882, Japan.
出版信息
Lung Cancer. 2021 Sep;159:162-170. doi: 10.1016/j.lungcan.2021.07.009. Epub 2021 Jul 18.
OBJECTIVES
This first-in-human phase I study (NCT03179436) investigated anti-cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody quavonlimab and anti-programmed death 1 monoclonal antibody pembrolizumab in patients with advanced solid tumors. The study was conducted in two parts: dose-escalation (part 1) and dose-confirmation (part 2). First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well tolerated (grade ≥ 3 treatment-related adverse events [TRAEs] were lowest with quavonlimab 25 mg every 6 weeks [Q6W] at 30% and highest with quavonlimab 75 mg Q3W at 57%) in non-small cell lung cancer. We present data from patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy.
MATERIALS AND METHODS
Patients with stage III/IV SCLC received quavonlimab 75 mg Q6W plus pembrolizumab 200 mg Q3W for ≤ 2 years. Primary endpoints were safety and tolerability; ORRs as assessed by blinded independent central review per Response Evaluation Criteria In Solid Tumorsv1.1 was a secondary endpoint. Progression-free survival (PFS), overall survival (OS), and the correlation of response with PD-L1 expression were exploratory endpoints.
RESULTS
Forty patients with extensive-stage SCLC received treatment; median follow-up was 13 months. Dose-limiting toxicity occurred in 4 patients (10%). TRAEs occurred in 80% of patients; grade 3 events occurred in 33% of patients and no grade 4/5 events were reported. Confirmed ORRs (95% CI) were 18% (7-33) among all patients, 7% (<1-34) for PD-L1-positive tumors (n = 14), and 19% (5-42) for PD-L1-negative tumors (n = 21). Response duration ranged from 2.9 to 19.1+ months. Median PFS was 2.0 months; 6-month PFS rate was 26%. Median OS was 11.0 months; 6-month OS rate was 66%.
CONCLUSIONS
Encouraging antitumor activity was observed with quavonlimab + pembrolizumab in patients with extensive-stage SCLC; responses were observed in PD-L1-positive and PD-L1-negative tumors. The combination was tolerable with manageable toxicities.
目的
本首次人体 I 期研究（NCT03179436）调查了抗细胞毒性 T 淋巴细胞相关蛋白 4 单克隆抗体 quavonlimab 和抗程序性死亡 1 单克隆抗体 pembrolizumab 在晚期实体瘤患者中的作用。该研究分为两部分：剂量递增（第 1 部分）和剂量确认（第 2 部分）。在非小细胞肺癌患者中，采用 quavonlimab + pembrolizumab 一线治疗显示出令人鼓舞的抗肿瘤活性（客观缓解率 [ORR]为 28%-40%），且总体耐受性良好（最高的 57%为 quavonlimab 75mg Q3W，最低的为 30%为 quavonlimab 25mg Q6W）。我们报告了接受二线或后线治疗的广泛期小细胞肺癌（SCLC）患者的数据。
材料和方法
III/IV 期 SCLC 患者接受 quavonlimab 75mg Q6W 加 pembrolizumab 200mg Q3W 治疗，治疗时间不超过 2 年。主要终点为安全性和耐受性；盲法独立中心评估的按实体瘤反应评价标准 1.1 评估的 ORR 为次要终点。无进展生存期（PFS）、总生存期（OS）和反应与 PD-L1 表达的相关性为探索性终点。
结果
40 例广泛期 SCLC 患者接受了治疗；中位随访时间为 13 个月。4 例（10%）患者发生剂量限制毒性。80%的患者发生 TRAE；33%的患者发生 3 级事件，无 4/5 级事件报告。所有患者的确认 ORR（95%CI）为 18%（7-33），PD-L1 阳性肿瘤为 7%（<1-34），PD-L1 阴性肿瘤为 19%（5-42）。反应持续时间为 2.9 至 19.1+ 个月。中位 PFS 为 2.0 个月；6 个月 PFS 率为 26%。中位 OS 为 11.0 个月；6 个月 OS 率为 66%。
结论
在广泛期 SCLC 患者中，观察到 quavonlimab + pembrolizumab 具有令人鼓舞的抗肿瘤活性；在 PD-L1 阳性和 PD-L1 阴性肿瘤中均观察到反应。该联合方案具有可管理的毒性，且耐受性良好。
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