Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
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DOI：
10.1007/s00280-016-3237-x
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发表时间：
2017-04
影响因子：
3
通讯作者：
Yokota K
中科院分区：
文献类型：
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作者：
Yamazaki N;Takenouchi T;Fujimoto M;Ihn H;Uchi H;Inozume T;Kiyohara Y;Uhara H;Nakagawa K;Furukawa H;Wada H;Noguchi K;Shimamoto T;Yokota K
这项 I b 期研究评估了派姆单抗在日本晚期黑色素瘤患者中的安全性和抗肿瘤活性。帕博利珠单抗 (2 mg/kg) 每 3 周 (Q3W) 给药一次，持续长达 2 年或直至确认进展或出现不可接受的毒性。肿瘤反应根据实体瘤反应评估标准 1.1 版 (RECIST v1.1) 通过研究者审查和中央审查进行评估。 42 名晚期黑色素瘤患者接受了派姆单抗治疗。 34 名患者（81.0%）观察到原发性皮肤组织学，8 名患者（19.0%）观察到原发性粘膜组织学。 34 名患者 (81.0%) 经历了治疗相关的不良事件 (AE)。最常见的治疗相关不良事件是瘙痒、斑丘疹、不适和甲状腺功能减退。 8 名患者 (19.0%) 发生了 3-5 级治疗相关 AE。至少两名患者报告的唯一 3-5 级治疗相关 AE 是贫血。有两例与治疗相关的死亡（原因不明和脑出血）。在 37 名可评估的患者中，经中心审查确定的皮肤黑色素瘤总缓解率 (ORR) 为 24.1% (95% CI 10.3–43.5)，粘膜黑色素瘤为 25.0% (95% CI 3.2–65.1)。这些反应是持久的，并且两个人群都没有达到中位反应持续时间。中位总生存期 (OS) 尚未达到，皮肤黑色素瘤的 12 个月 OS 为 82.7%，粘膜黑色素瘤为 51.4%。日本患者中派姆单抗的安全性与之前的临床研究报告相似。 Pembrolizumab 对日本晚期黑色素瘤患者具有良好的抗肿瘤活性。
This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3–5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3–5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3–43.5) for cutaneous melanoma and 25.0% (95% CI 3.2–65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma. The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.