Peter MacCallum Cancer Centre, Melbourne, 8006, Australia.
Nucleus Network, Melbourne, 3004, Australia.
Immunotherapy. 2024;16(11):759-774. doi: 10.1080/1750743X.2024.2359359. Epub 2024 Sep 12.
This first-in-human study evaluated safety and efficacy of CD40 agonist MEDI5083 with durvalumab in patients with advanced solid tumors. Patients received MEDI5083 (3-7.5 mg subcutaneously every 2 weeks × 4 doses) and durvalumab (1500 mg every 4 weeks) either sequentially (N = 29) or concurrently (N = 9). Primary end point was safety; secondary end points included efficacy. Thirty-eight patients received treatment. Most common adverse events (AEs) were injection-site reaction (ISR; sequential: 86%; concurrent: 100%), fatigue (41%; 33%), nausea (20.7%; 55.6%) and decreased appetite (24.1%; 33.3%). Nine patients had MEDI5083-related grade ≥3 AEs with ISR being the most common. Two patients experienced dose limiting toxicities (ISR). One death occurred due to a MEDI5083-related AE. MEDI5083 maximum tolerated dose was 5 mg. Objective response rate was 2.8% (1 partial response and 11 stable disease). MEDI5083 toxicity profile limits its further development.
这项首次人体研究评估了 CD40 激动剂 MEDI5083 与 durvalumab 联合用于晚期实体瘤患者的安全性和疗效。患者接受 MEDI5083（皮下每 2 周 3-7.5 毫克，共 4 剂）和 durvalumab（每 4 周 1500 毫克）序贯（N=29）或同时（N=9）给药。主要终点是安全性；次要终点包括疗效。38 名患者接受了治疗。最常见的不良反应（AE）是注射部位反应（ISR；序贯：86%；同时：100%）、疲劳（41%；33%）、恶心（20.7%；55.6%）和食欲下降（24.1%；33.3%）。9 名患者发生了 MEDI5083 相关的≥3 级 AE，ISR 是最常见的。2 名患者发生了剂量限制性毒性（ISR）。1 例死亡与 MEDI5083 相关的 AE 有关。MEDI5083 的最大耐受剂量为 5 毫克。客观缓解率为 2.8%（1 例部分缓解和 11 例疾病稳定）。MEDI5083 的毒性谱限制了其进一步发展。
