HF10, an attenuated, replication-competent mutant strain of Herpes Simplex Virus type 1 (HSV-1), is a promising new oncolytic viral immunotherapy. HF10 (intratumoral injection) showed activity in injected lesions and uninjected lesions in the preclinical and the clinical. To assess the safety and tolerability of HF10, we conducted a Phase I trial in the Japanese patients with refractory solid tumors with cutaneous and/or superficial lesions.
The study was an open label, non-randomized, dose escalation study evaluating 2 dose levels of HF10 (1 x 106, 1 x 107 TCID50/dose). Dose escalation proceeded according to a “3 + 3” design. HF10 injected into single lesion up to 4 injections (≥ 2 weeks apart). Adverse events (AEs) were evaluated according to NCI CTCAE v4.0. Evaluation criteria at sequential timepoints included overall and injected tumor response per mWHO criteria; safety; viral detection by qPCR.
Six patients (pts) with melanoma or other skin cancers were enrolled and treated. Of 6 safety evaluable pts, no DLTs were reported. HF10-related AEs occurred in 3 pts (Grade 1 Malaise in 2pts, Gr 1 Headache and Gr 1 Abdominal pain lower in 1 pt). These AEs were easily managed, and no HF10-related serious AEs were reported. Of 6 efficacy evaluable pts, 4 pts showed SD and 2 pts showed PD. One pt with vaginal melanoma had pigmented-lesion faded during the HF10 treatment, and showed SD (16.7% decrease) at the end of study. Moreover, the pt started PD-1 treatment soon after HF10, and finally reached CR.
Multiple intratumoral injections of HF10 in superficial tumors was well-tolerated and appeared to be safe. Also, HF10 injection resulted in stabilization of the injected tumor. Comparing the results from the Phase I in the US, it was considered that there was no significant difference in the safety profile between the US and Japanese pts.
Clinical trial identification
Legal entity responsible for the study
Takara Bio, Inc.
Takara Bio, Inc.
N. Yamazaki: Receipt of honorarium from Takara Bio, Inc.
All other authors have declared no conflicts of interest.