Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors
Mené sur 16 patients atteints d'un cancer non hématologique de stade avancé (âge médian : 62,5 ans), cet essai de phase Ib évalue la sécurité d'un traitement combinant une injection intratumorale de C. novyi-NT et du pembrolizumab
Purpose: Intratumoral injection of Clostridium novyi-NT, lacking alpha toxin, germinates and subsequently replicates in the tumor hypoxic regions, causing cell lysis and inflammation. This phase 1b study investigated the safety and synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors.
Experimental Design: Patients with injectable solid tumors received one intratumoral (IT) C. novyi-NT injection (Day 8) across four dose cohorts (3x104 to 100x104 spores) with pembrolizumab (200mg intravenous (IV) every 3 weeks, Day 0 to 24 months). Sixteen patients were enrolled with a median age of 62.5 years and the most common tumor types being breast cancer and melanoma.
Results: The combination therapy demonstrated a manageable safety profile, with one grade 3 dose-limiting toxicity (DLT) of abscess formation and the remainder of treatment-related adverse events (TRAEs) 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 (MTD) was determined as pembrolizumab IV 200mg every 3 weeks and a single dose of 100x104 C.novyi-NT spores IT on Day8. The confirmed overall objective response rate of 25%(n=4) was observed among patients with undifferentiated nasopharyngeal squamous carcinoma, squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma. Among these patients we obtained 3 partial responses and one complete response. Median duration of response was 10.93 months, and stable disease was observed in 69% patients.
Conclusion: This study highlights the potential of the C. novyi-NT and pembrolizumab combination as a promising therapeutic strategy for treatment-refractory solid tumors.
Clinical Cancer Research , article en libre accès, 2025