KEYNOTE-199 (NCT02787005) 是一项多队列 2 期研究，评估派姆单抗治疗转移性去势抵抗性前列腺癌 (mCRPC) 患者的效果。队列 4 (C4) 和队列 5 (C5) 的结果已公布。符合条件的患者未接受 mCRPC 化疗，并且根据前列腺癌临床试验工作组 3 指南的定义，在出现耐药性之前对恩杂鲁胺有反应。患有 RECIST 可测量疾病的患者纳入 C4，仅患有骨疾病或骨为主疾病的患者纳入 C5。所有患者每 3 周接受 200mg 派姆单抗治疗，持续 ≤35 个周期，并持续使用恩杂鲁胺，直至出现进展、出现不可接受的毒性或停药。主要终点是 C4 中盲法独立中央审查根据 RECIST v1.1 得出的客观缓解率 (ORR)。次要终点包括每个队列和两个队列组合的疾病控制率 (DCR)、总生存率和安全性。总共有 126 名患者接受治疗（C4，n = 81；C5，n = 45）。中位年龄为 72 岁（范围 43-92），87.3% 在进入研究前已接受恩杂鲁胺治疗 ≥6 个月。 C4 的确认 ORR 为 12.3% (95% CI 6.1-21.5%)。 C4 的中位缓解持续时间为 8.1 个月（范围为 2.5 至 15.2 个月），其中 5 名患者出现了持续≥6 个月的客观缓解。 C4 中的 DCR 为 53.1% (95% CI 41.7-64.3%)，C5 中的 DCR 为 51.1% (95% CI 35.8-66.3%)。 C4 中位总生存期为 17.6 个月（95% CI 14.0-22.6），C5 中位总生存期为 20.8 个月（95% CI 14.1-28.9）。 35名患者（27.8%）发生≥3级治疗相关不良事件； C4 中的 2 名患者死于免疫相关不良事件（肌无力综合征和吉兰-巴利综合征）。对于接受恩杂鲁胺治疗后病情进展的 mCRPC 患者，在正在进行的恩杂鲁胺治疗中添加派姆单抗显示出适度的抗肿瘤活性，且安全性可控。 ClinicalTrials.gov, NCT02787005.© 2024。这是美国政府的作品，在美国不受版权保护；外国版权保护可能适用。

KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43-92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1-21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7-64.3%) in C4 and 51.1% (95% CI 35.8-66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0-22.6) in C4 and 20.8 months (95% CI 14.1-28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.ClinicalTrials.gov, NCT02787005.© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.