肿瘤内注射维多利莫德单药治疗或与帕博利珠单抗联合治疗程序性细胞死亡蛋白1阻断耐药黑色素瘤患者：1b期研究的最终分析

Intratumoral vidutolimod as monotherapy or in combination with pembrolizumab in patients with programmed cell death 1 blockade-resistant melanoma: Final analysis from a phase 1b study.

作者信息

Milhem Mohammed M, Zakharia Yousef, Davar Diwakar, Buchbinder Elizabeth I, Medina Theresa, Daud Adil, Ribas Antoni, Chmielowski Bartosz, Niu Jiaxin, Gibney Geoffrey T, Margolin Kim, Olszanski Anthony J, Mehmi Inderjit, Sato Takami, Shaheen Montaser, Zhao Luping, Kelley Heather, Liu Hong, Kumar Sujatha, Bobilev Dmitri, Krieg Arthur M, Wooldridge James E, Kirkwood John M

机构信息

University of Iowa, Iowa City, Iowa, USA.

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

出版信息

Cancer. 2025 Aug 1;131(15):e70022. doi: 10.1002/cncr.70022.

DOI:10.1002/cncr.70022

PMID:40753466

Abstract

BACKGROUND

New treatment options are needed for patients with metastatic anti-programmed cell death 1 (PD-1)-resistant melanoma. The final analysis of a phase 1b study evaluating the Toll-like receptor 9 agonist vidutolimod is reported here.

METHODS

This two-part, open-label, multicenter, phase 1b study in adults with metastatic/unresectable anti-PD-1-resistant melanoma evaluated the safety and clinical activity of intratumoral vidutolimod plus systemic pembrolizumab (part 1) or vidutolimod alone (part 2). Two vidutolimod formulations were evaluated with different concentrations of polysorbate (PS20-A, 0.005%-0.01% polysorbate 20; PS20-B, 0.00167% polysorbate 20). Key end points were safety and investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors, version 1.1).

RESULTS

A total of 159 patients were treated in part 1 (PS20-A, n = 98; PS20-B, n = 61), and 40 patients were treated in part 2. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100.0% of patients. Grade ≥3 TEAEs occurred in 55.3% (part 1) and 37.5% (part 2) of patients. No treatment-related deaths occurred. Best ORR was 23.5% (95% CI, 15.5%-33.1%; complete response [CR], 7.1%) for vidutolimod PS20-A plus pembrolizumab, 11.5% (95% CI, 4.7%-22.2%; CR, 1.6%) for vidutolimod PS20-B plus pembrolizumab, and 20.0% (95% CI, 9.1%-35.6%) for vidutolimod monotherapy. Median duration of response was 25.2 months with vidutolimod PS20-A plus pembrolizumab, 11.4 months with vidutolimod PS20-B plus pembrolizumab, and 5.6 months with vidutolimod monotherapy.

CONCLUSIONS

Vidutolimod PS20-A alone or in combination with pembrolizumab had an acceptable safety profile and promising clinical activity in patients with PD-1 blockade-resistant melanoma.

摘要

背景

转移性抗程序性细胞死亡蛋白1（PD-1）耐药黑色素瘤患者需要新的治疗选择。本文报告了一项评估Toll样受体9激动剂维杜利莫德的1b期研究的最终分析结果。

方法

这项分为两部分的开放标签多中心1b期研究纳入了患有转移性/不可切除的抗PD-1耐药黑色素瘤的成人患者，评估瘤内注射维杜利莫德联合全身使用派姆单抗（第1部分）或单独使用维杜利莫德（第2部分）的安全性和临床活性。评估了两种不同聚山梨酯浓度的维杜利莫德制剂（PS20-A，0.005%-0.01%聚山梨酯20；PS20-B，0.00167%聚山梨酯20）。主要终点为安全性和研究者评估的客观缓解率（ORR；实体瘤疗效评价标准，1.1版）。

结果

第1部分共治疗了159例患者（PS20-A组，n = 98；PS20-B组，n = 61），第2部分治疗了40例患者。100.0%的患者发生了任何级别的治疗中出现的不良事件（TEAE）。≥3级TEAE分别发生在55.3%（第1部分）和37.5%（第2部分）的患者中。未发生与治疗相关的死亡。维杜利莫德PS20-A联合派姆单抗的最佳ORR为23.5%（95%CI，15.5%-33.1%；完全缓解[CR]，7.1%），维杜利莫德PS20-B联合派姆单抗的最佳ORR为11.5%（95%CI，4.7%-22.2%；CR，1.6%），维杜利莫德单药治疗组的最佳ORR为20.0%（95%CI，9.1%-35.6%）。维杜利莫德PS20-A联合派姆单抗的中位缓解持续时间为25.2个月，维杜利莫德PS20-B联合派姆单抗的中位缓解持续时间为11.4个月，维杜利莫德单药治疗的中位缓解持续时间为5.6个月。