A phase II open label, randomized clinical trial of atezolizumab with or without human recombinant IL-7 (CYT107) in advanced urothelial cancer

阿替唑单抗 医学 肿瘤科 不利影响 内科学 临床研究阶段 癌症 免疫疗法 临床试验 泌尿科 彭布罗利珠单抗
作者
Randy F. Sweis,Gurkamal Chatta,Rohit K. Jain,Helen Moon,Scott E. Delacroix,Alana Fang,Leonard D’Amico,Angela Shaulov Kask,Martin A. Cheever,Steven P. Fling,Elad Sharon,Andreanne M. Lacroix,Judith C. Kaiser,Russell K. Pachynski,Evan Y. Yu
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
标识
DOI:10.1158/1078-0432.ccr-24-1728
摘要

Abstract Purpose: Advanced urothelial cancer generally has high mortality despite modern anti-PD-1/L1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (CITN-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses. Patients and Methods: Patients with urothelial cancer following platinum chemotherapy were randomized to atezolizumab alone or with CYT107 weekly for four doses. The primary objective was clinical efficacy by objective response rate (ORR). Secondary objectives included safety, toxicity, and other clinical outcomes. Correlative endpoints included peripheral immunophenotyping and quantification of cytokines. Results: CYT107 plus atezolizumab was well-tolerated, without dose-limiting toxicities (DLTs), and lower grade 3-4 treatment-related adverse events (TRAEs) compared to atezolizumab. The ORR was 26.3% for the combination versus 23.8% for atezolizumab alone (p = 0.428). The complete response (CR) rate was 10.5% for the combination versus 4.8% for monotherapy. Three patients on the combination had responses >21 months versus one with monotherapy. CD4+ and CD8+ T lymphocyte expansion occurred in patients with response to combination therapy, with the greatest effect in T memory stem cell (Tscm) cells. Responding patients had elevated baseline CCL4 and decreased VEGF-A and TNF. Conclusions: Combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, a doubling of the CR rate, and durable responses exceeding 2 years, however, the ORR was similar to atezolizumab alone. Increased and sustained doses of CYT107 coupled with patient selection strategies should be further investigated.
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