Intratumoral injection of Clostridium novyi-NT spores in patients with treatment-refractory advanced solid tumors Journal Article
| Authors: | Janku, F.; Zhang, H. H.; Pezeshki, A.; Goel, S.; Murthy, R.; Wang-Gillam, A.; Shepard, D. R.; Helgason, T.; Masters, T.; Hong, D. S.; Piha-Paul, S. A.; Karp, D. D.; Klang, M.; Huang, S. Y.; Sakamuri, D.; Raina, A.; Torrisi, J.; Solomon, S. B.; Weissfeld, A.; Trevino, E.; DeCrescenzo, G.; Collins, A.; Miller, M.; Salstrom, J. L.; Korn, R. L.; Zhang, L.; Saha, S.; Leontovich, A. A.; Tung, D.; Kreider, B.; Varterasian, M.; Khazaie, K.; Gounder, M. M. |
| Article Title: | Intratumoral injection of Clostridium novyi-NT spores in patients with treatment-refractory advanced solid tumors |
| Abstract: | 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 1⁄4 2) and grade 4 gas gangrene (n 1⁄4 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n 1⁄4 1), limb abscess (n 1⁄4 1), soft-tissue infection (n 1⁄4 1), respiratory insufficiency (n 1⁄4 1), and rash (n 1⁄4 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. © 2020 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 27 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-01-01 |
| Start Page: | 96 |
| End Page: | 106 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-20-2065 |
| PROVIDER: | scopus |
| PUBMED: | 33046513 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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