Candel Therapeutics, Inc. announced the presentation of updated data from an ongoing phase 1b clinical trial of its herpes simplex virus-1 (HSV-1) replication-competent viral immunotherapy candidate, CAN-3110, in patients with rHGG that has recurred after standard of care (SoC) treatment. The data were presented during the 5th Glioblastoma Drug Development Summit in Boston, Massachusetts. To date, over 50 patients have been treated with a single dose of CAN-3110 in the phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma (rHGG).

The investigators observed a nearly doubling of the expected median overall survival (mOS) after a single CAN-3110 injection, achieving a mOS of ~12 months, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. Positive HSV-1 serology was a predictor of response and was associated with improved survival (mOS in this population reached 14 months). Results from the ongoing phase 1b clinical trial were published in Nature in Fourth Quarter 2023.

CAN-3110 received U.S. Food and Drug Administration (FDA) Fast Track Designation for treatment of rHGG in First Quarter 2024, based on these data. The clinical trial comprises three arms. In arm A, 41 patients with recurrent HGG received a single intratumoral injection of CAN-3110 (dose ranging from 1x106 plaque forming units (pfu) to 1x1010 pfu), including nine patients with multifocal/multicentric, deep or bilateral tumors associated with poor survival. After observing this regimen was generally well tolerated without dose-limiting toxicity, patients in arm B (n=9) received a single dose of cyclophosphamide (24 mg/kg) two days before CAN-3110 injection at doses of 1 x 108 pfu (n=3) and 1 x 109 pfu (n=6).

The rationale is based on findings in mouse models, where cyclophosphamide improved viral persistence in injected tumors. In arm C, two cohorts of 12 patients with rHGG will receive up to six injections of CAN-3110 over a four-month period. CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation in a single therapeutic.

Its activity is designed to be conditional to the expression of Nestin in cancer cells. CAN-3110 is being evaluated in a phase 1 investigator-sponsored clinical trial in patients with rHGG. In October 2023, the Company announced that Nature published results from this ongoing clinical trial.

CAN-3110 was well tolerated with no dose-limiting toxicity reported and CAN-3110 plus prodrug was associated with improved survival. Positive HSV-1 serology was a predictor of response and was associated with improved survival. Increased infiltrating immune cells in the tumor microenvironment and expansion of the T cell repertoire after treatment were also associated with improved survival.

In the clinical trial, the investigators observed a nearly doubling of the expected median overall survival after a single CAN-3110 injection, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. By comparison, survival in the anti-HSV1 positive patients who received CAN-3110 was more than 14 months.