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：Mohammed Milhem, Yousef Zakharia, Diwakar Davar, Elizabeth I. Buchbinder, Theresa Medina, Adil Daud, Antoni Ribas, Bartosz Chmielowski, Jiaxin Niu, Geoffrey T. Gibney, Kim Margolin, Anthony J. Olszanski, Inderjit Mehmi, Takami Sato, Montaser Shaheen, Luping Zhao, Heather Kelley, Hong Liu, Sujatha Kumar, Dmitri Bobilev, Arthur Μ. Krieg, James E. Wooldridge, John M. Kirkwood · 发表于：Cancer · 年份：2025 · DOI：10.1002/cncr.70022 · 被引用次数：3 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Melanoma and MAPK Pathways

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 wi...