Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT02428036.

Legal entity responsible for the study

Takara Bio, Inc.

Funding

Takara Bio, Inc.

Disclosure

N. Yamazaki: Receipt of honorarium from Takara Bio, Inc.

All other authors have declared no conflicts of interest.

Background

To elucidate the etiology of skin malignancy in people in the hamlet of Kiradalli, Yadgir District, Karnataka State, India, where many people experienced skin lesions that transformed into malignancy.

Methods

A cross-sectional survey of the inhabitants of Kiradalli was performed by trained and supervised paramedics. Skin lesions were documented. Lesions with a high suspicion of malignancy underwent biopsy. Drinking water was analyzed at the Cochin University of Science and Technology for arsenic content. Blood of affected patients was sent for arsenic level estimation and compared with normal levels. The media and social activists were involved to highlight this community health issue to help provide an alternative source of water and to provide rehabilitation.

Results

Forty-six people were found to have skin changes suspicious for arsenic keratosis. Ten cases of epidermal malignancy were noted. A prevalence of 2.38% for epidermal neoplasm and 10.9% for arsenic keratosis was documented. The arsenic level of the water was 0.483 mg/L—much higher than the permitted level. Arsenic in the blood of affected patients was high. Among 10 cases, 9 cases are alive and 1 patient died of cardiac cause.

Conclusions

Arsenic in the drinking water as a cause of skin cancer was established. The primary preventative measure to halt the development of new lesions was to provide safe drinking water for residents. The secondary preventative measure was to improve the prognosis of patients with malignant lesions by early diagnosis and treatment.

Legal entity responsible for the study

self.

Funding

None

Disclosure

All authors have declared no conflicts of interest.