Paris-Saclay University, Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France.
Oncology Department, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona.
Ann Oncol. 2023 Oct;34(10):920-933. doi: 10.1016/j.annonc.2023.07.006. Epub 2023 Sep 11.
Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients.
ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks.
Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002).
In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.
接受免疫检查点抑制剂 (ICB) 治疗的晚期非小细胞肺癌 (NSCLC) 患者最终会出现快速进展（原发性耐药）或在持久获益后进展（继发性耐药）。癌症疫苗 OSE2101 可能会在 ICB 失败后增强抗肿瘤特异性免疫反应。ATALANTE-1 的目的是评估其在这些患者中的疗效和安全性。
ATALANTE-1 是一项两步开放性标签研究，旨在评估 OSE2101 与标准治疗 (SoC) 化疗 (CT) 相比的疗效和安全性。人类白细胞抗原 (HLA)-A2 阳性、无可操作改变的晚期 NSCLC 患者，在接受序贯或同期 CT 和 ICB 治疗后出现进展，按 2:1 比例随机分配至 OSE2101 或 SoC（多西他赛或培美曲塞）。主要终点是总生存期 (OS)。根据 Fleming 设计计划进行 OS 无效性的中期分析。2020 年 4 月，在中期分析时，由于 2019 年冠状病毒病 (COVID-19) 的原因，决定提前停止入组。所有患者和 ICB 二线继发性耐药亚组（二线 ICB 单药治疗后 12 周以上进展）进行了最终分析。
219 名患者被随机分配（OSE2101 组 139 例，SoC 组 80 例）；118 例患者对序贯 ICB 具有继发性耐药性。总体而言，OSE2101 组的中位 OS 非显著优于 SoC 组 [风险比 (HR) [95%置信区间 (CI)] 0.86 [0.62-1.19]，P=0.36]。在二线继发性耐药亚组中，OSE2101 组与 SoC 组相比，中位 OS 显著改善[11.1 个月与 7.5 个月；HR (95%CI) 0.59 (0.38-0.91)，P=0.017]，并且显著改善了疾病进展后的生存期 (HR 0.46，P=0.004)、ECOG 表现状态恶化的时间 (HR 0.43，P=0.006) 和 QLQ-C30 全球健康状况评分 (与 SoC 相比，P=0.045)。两组的 6 个月疾病控制率和无进展生存期相似。OSE2101 组发生≥3 级不良事件的患者为 11.4%，SoC 组为 35.1%（P=0.002）。
在 HLA-A2 阳性、对免疫治疗具有继发性耐药性的晚期 NSCLC 患者中，与 CT 相比，OSE2101 增加了生存时间，且安全性更好。需要进一步评估该人群。
