Intratumoral Clostridium Novyi-Nontoxic Plus Pembrolizumab Demonstrates Clinical Promise Among Patients With Treatment-Refractory Advanced Solid Tumors
According to results from a phase 1b study, clostridium novyi-nontoxic (C. novyi-NT) plus pembrolizumab demonstrated clinical promise among patients with treatment-refractory advanced solid tumors.
“Intratumoral injection of C. novyi-NT, lacking alpha-toxin, germinates and subsequently replicates in the tumor hypoxic regions, causing cell lysis and inflammation,” stated Blessie Elizabeth Nelson, MD, MD Anderson Cancer Center, Houston, Texas, and coauthors. “This phase Ib study investigated the safety and synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors.”
In this study, researchers enrolled 16 patients with solid tumors including nonkeratinizing undifferentiated nasopharyngeal squamous carcinoma, human papilloma virus (HPV)-positive squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma. Patients were assigned to receive either 3 x 104 or 100 x 104 spores of intratumoral C. novyi-NT plus 200 mg of pembrolizumab once every 3 weeks. The primary end point was the maximum tolerated dose. Key secondary end points included objective response rate (ORR), duration of response, and safety.
At analysis, the maximum tolerated dose of C. novyi-NT was 100 x 104. A confirmed ORR of 25% was observed in 4 patients with 3 partial responses and 1 complete response. The median duration of response was 10.93 months. Stable disease was observed in 69% of patients. The most frequently observed grade 3 dose-limiting toxicity was abscess formation. Treatment-related adverse events occurring in ≥ 10% of patients included injection site reaction (25%), pyrexia (19%), pruritus (13%), leukopenia (13%), and anemia (13%).
“This study highlights the potential of the C. novyi-NT and pembrolizumab combination as a promising therapeutic strategy for treatment-refractory solid tumors,” concluded Dr Nelson et al.
Source:
Nelson BE, Janku F, Fu S, et al. Phase Ib study of pembrolizumab in combination with intratumoral injection of clostridium novyi-NT in patients with advanced solid tumors. Clin Cancer Res. Published online: August 12, 2025. doi:10.1158/1078-0432.CCR-24-3952
