Background Intratumorally injected Clostridium novyi-NT (non-toxic), an attenuated strain of C. novyi that lacks production of the lethal alpha toxin, replicates within hypoxic tumor regions and elicits tumor-confined cell lysis. Early clinical and translational data suggest that intratumoral injection of C. novyi-NT is feasible, demonstrates early signals of anti-tumor activity and induction of the host immune response, which supports additional studies in combination with immune checkpoint inhibitors.

Methods This first-in-human study (NCT03435952) enrolls patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 4 dose cohorts (3 × 104 to 100 × 104 spores, 3+3 dose-escalation design) in combination with intravenous pembrolizumab 200 mg every 3 weeks for up to 24 months to determine dose-limiting toxicities (DLTs), and the maximum tolerated dose (MTD).

Results As of August 24, 2020, 9 patients (breast cancer, n=2; colorectal cancer, n=1; fibrous histiocytoma, n=1; anal cancer, n=1; chondrosarcoma, n=1; appendiceal cancer, n=1; tongue squamous cell cancer, n=1; nasopharyngeal cancer, n=1) were treated. There were no DLTs to date. Signs and symptoms of C. novyi-NT germination (infection) including fever, injection site pain, erythema, swelling, tenderness, and in some cases, ulceration, spontaneous drainage, tissue sloughing, bleeding, and malodor were observed in 5 patients. Partial responses were noted in 2 of 9 patients (tongue squamous cell cancer, nasopharyngeal cancer).

Conclusions Single intratumoral injection of C. novyi-NT in combination with pembrolizumab has been demonstrating manageable toxicity profile and encouraging signals of anticancer activity. The enrolment continues.

Trial Registration NCT03435952

Ethics Approval The study was approved by MD Anderson IRB