A phase 1 study of the CD40 agonist MEDI5083 in combination with durvalumab in patients with advanced solid tumors.

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunotherapy Pub Date : 2024-09-12 DOI:10.1080/1750743x.2024.2359359

Ben Tran,Mark Voskoboynik,Johanna Bendell,Martin Gutierrez,Charlotte Lemech,Daphne Day,Sophia Frentzas,Ignacio Garrido-Laguna,Nathan Standifer,Fujun Wang,Charles Ferte,Yue Wang,Mayukh Das,Benedito A Carneiro

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引用次数: 0

Abstract

Aim: This first-in-human study evaluated safety and efficacy of CD40 agonist MEDI5083 with durvalumab in patients with advanced solid tumors.Methods: 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.Results: 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).Conclusion: MEDI5083 toxicity profile limits its further development.

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CD40 激动剂 MEDI5083 联合 durvalumab 治疗晚期实体瘤患者的 1 期研究。

目的：这一首次人体试验评估了CD40激动剂MEDI5083与durvalumab在晚期实体瘤患者中的安全性和有效性：患者依次（29 例）或同时（9 例）接受 MEDI5083（3-7.5 毫克，每 2 周皮下注射一次 × 4 次）和 durvalumab（1500 毫克，每 4 周一次）治疗。主要终点是安全性，次要终点包括疗效：结果：38名患者接受了治疗。最常见的不良事件（AEs）为注射部位反应（ISR；序贯：86%；并发：100%）、疲劳（41%；33%）、恶心（20.7%；55.6%）和食欲下降（24.1%；33.3%）。9名患者出现了与MEDI5083相关的≥3级AE，其中最常见的是ISR。两名患者出现了剂量限制性毒性反应（ISR）。一名患者因 MEDI5083 相关 AE 死亡。MEDI5083的最大耐受剂量为5毫克。客观反应率为2.8%（1例部分反应和11例疾病稳定）：结论：MEDI5083的毒性特征限制了其进一步发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunotherapy 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

113

审稿时长

6-12 weeks

期刊介绍： Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field. Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.