START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain.
University Hospital INCLIVA, Valencia, Spain.
Clin Lung Cancer. 2022 Nov;23(7):e415-e427. doi: 10.1016/j.cllc.2022.05.013. Epub 2022 May 23.
Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284).
Here, we report an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1-4, then 1000 mg Q6W) until disease progression or unacceptable toxicity for > 2 years. The primary endpoints were immune-related objective response rate (irORR) per investigator-assessed irRECIST and safety.
As of 8, July 2019, 67 patients with recurrent/advanced NSCLC were enrolled and treated with dostarlimab; the majority had programmed death ligand 1 (PD-L1) tumor proportion score (TPS) < 1% (35.8% of patients) or PD-L1 TPS 1%-49% (29.9% of patients); 7.5% had PD-L1 TPS ≥ 50%, and 26.9% had unknown PD-L1 TPS status. Median follow-up was 13.8 months (range: 0.0-22.6). irORR was 26.9%, including 2 complete and 16 partial responses. The median duration of response of 11.6 months (range: 2.8-19.4). Responses were observed in 2 of 24 (16.7%) patients with PD-L1 TPS < 1%, 4 of 20 (20.0%) patients with PD-L1 TPS 1%-49% and 2 of 5 (40.0%) patients with PD-L1 TPS ≥ 50%. Fatigue (4.5%) was the most common Grade ≥ 3 treatment-related treatment-emergent adverse event (TRAE). Immune-related TRAEs (any grade) were observed in 28.4% of patients.
Dostarlimab demonstrated promising antitumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, including across all PD-L1 subgroups, and has an acceptable safety profile.
Dostarlimab 是一种抗程序性死亡蛋白-1 抗体，正在复发/晚期实体瘤中进行评估，包括非小细胞肺癌（NSCLC），正在进行的 I 期、多中心、开放标签、2 部分（剂量递增和队列扩展）GARNET 研究（NCT02715284）。
在这里，我们报告了一项复发/晚期 NSCLC 患者的中期分析，这些患者在铂类化疗后进展。患者接受 dostarlimab（第 1-4 周期每 3 周静脉注射 500mg[Q3W]，然后每 6 周静脉注射 1000mg），直至疾病进展或不可接受的毒性持续超过 2 年。主要终点是研究者评估的免疫相关客观缓解率（irORR）和安全性。
截至 2019 年 7 月 8 日，67 例复发/晚期 NSCLC 患者入组并接受 dostarlimab 治疗；大多数患者的程序性死亡配体 1（PD-L1）肿瘤比例评分（TPS）<1%（35.8%的患者）或 PD-L1 TPS 1%-49%（29.9%的患者）；7.5%的患者 PD-L1 TPS≥50%，26.9%的患者 PD-L1 TPS 状态未知。中位随访时间为 13.8 个月（范围：0.0-22.6）。irORR 为 26.9%，包括 2 例完全缓解和 16 例部分缓解。11.6 个月的中位缓解持续时间（范围：2.8-19.4）。在 PD-L1 TPS<1%的 24 例患者中观察到 2 例（16.7%），在 PD-L1 TPS 1%-49%的 20 例患者中观察到 4 例（20.0%），在 PD-L1 TPS≥50%的 5 例患者中观察到 2 例（40.0%）。最常见的≥3 级与治疗相关的治疗后出现的不良事件（TRAE）是疲劳（4.5%）。28.4%的患者出现免疫相关 TRAE（任何级别）。
在铂类化疗后进展的晚期/复发性 NSCLC 中，dostarlimab 显示出有希望的抗肿瘤活性，包括所有 PD-L1 亚组，且安全性可接受。
