Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi -NT in Patients with Advanced Solid Tumors

作者：Blessie Elizabeth Nelson, Filip Jankú, Siqing Fu, Ecaterina E. Dumbrava, David S. Hong, Daniel D. Karp, Aung Naing, Jordi Rodón, Apostolia M. Tsimberidou, Ravi Murthy, Rahul A. Sheth, Rodabe N. Amaria, Anthony P. Conley, Senthil Damodaran, Kanwal Raghav, Nicoleta Carapanceanu, Mahendra Pal Singh, Valentin Carapanceanu, Abdulmohammad Pezeshki, Alexey A. Leontovich, Brent L. Kreider, David Tung, Mary Varterasian, Khashayarsha Khazaie, Sarina A. Piha‐Paul · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-24-3952 · 被引用次数：8 · 研究领域：Cancer Research and Treatments、Clostridium difficile and Clostridium perfringens research、Cancer Immunotherapy and Biomarkers

PURPOSE: Intratumoral injection of Clostridium novyi-nontoxic (C. novyi-NT), lacking alpha-toxin, germinates and subsequently replicates in the tumor hypoxic regions, causing cell lysis and inflammation. This phase Ib study investigated the safety and synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors. PATIENTS AND METHODS: Patients with injectable solid tumors received one intratumoral C. novyi-NT injection (day 8) across four dose cohorts (3 × 104 to 100 × 104 spores) with pembrolizumab (200 mg intravenously every 3 weeks, day 0-24 months). Sixteen patients were enrolled with a median age of 62.5 years, and the most common tumor types were breast cancer and melanoma. RESULTS: The combination therapy demonstrated a manageable safety profile, with one grade 3 dose-limiting toxicity of abscess formation and the remainder of treatment-related adverse events in ≥10% of patients being grade 1 or 2 injection site reaction (25%), pyrexia (19%), pruritus (13%), leukopenia (13%), and anemia (13%). The maximum tolerated dose was determined to be pembrolizumab intravenously at 200 mg every 3 weeks and a single dose of 100 × 104C.novyi-NT spores intratumorally on day 8. The confirmed overall objective response rate of 25% was observed among four patients with nonkeratinizing undifferentiated nasopharyngeal squamous carcinoma, human papilloma virus-positive squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma. Among these patients, w...