Intratumoral injection of clostridium novyi-NT spores in patients with treatment-refractory advanced solid tumors

Filip Janku, Halle Huihong Zhang, Abdulmohammad Pezeshki, Sanjay Goel, Ravi Murthy, Andrea Wang-Gillam, Dale R. Shepard, Thorunn Helgason, Tyler Masters, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Mark Klang, Steven Y. Huang, Divya Sakamuri, Anjali Raina, Jean Torrisi, Stephen B. Solomon, Alice Weissfeld, Ernest TrevinoGary DeCrescenzo, Amanda Collins, Maria Miller, Jennifer L. Salstrom, Ronald L. Korn, Linping Zhang, Saurabh Saha, Alexey A. Leontovich, David Tung, Brent Kreider, Mary Varterasian, Khashayarsha Khazaie, Mrinal M. Gounder

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Purpose: Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation. Patients and Methods: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 104 to 3 106 spores, 3þ3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose. Results: Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n ¼ 2) and grade 4 gas gangrene (n ¼ 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n ¼ 1), limb abscess (n ¼ 1), soft-tissue infection (n ¼ 1), respiratory insufficiency (n ¼ 1), and rash (n ¼ 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses. Conclusions: Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalClinical Cancer Research
Issue number1
StatePublished - Jan 1 2021

ASJC Scopus subject areas

  • Medicine(all)


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