Background

Liver is a common metastatic site with poor prognosis for melanoma patients, yet limited efficacy has been shown in systemic therapy. OrienX010, a herpes simplex virus type 1-derived oncolytic immunotherapy with expression of gene encoding human GM-CSF, which has shown its efficacy in intralymphatic diseases, was tested for its safety and efficacy in phase Ic trial of intralesional injection into liver metastases.

Methods

OrienX010 (8 × 10⁷ pfu/ml, 10ml per injection) was given intralesionally by ultrasound guide q2w, dose was distributed into 1-2 liver lesions according to tumor size. Tumor assessment was done q8w by CT scan. The primary endpoint was toxicity, secondary endpoints included ORR, DCR and PFS time. Treatment continued until intolerance, or disease progression per iRECIST.

Results

From May 2016, 19 pts have been enrolled, 57.9% male with median age 47 years (32, 61). Mean size of injectable lesions was 30.4mm (10.0-59.0). One had c-Kit mutation (exon 9), no BRAF mutation. All pts had received at least one prior therapy, most (68.4%) were transcatheter hepatic arterial chemoembolization. 79.0% had multiple liver metastases, 57.9% had extrahepatic metastases including lung, bone, abdominal, and distant lymph node. 57.9% had an elevation of serum LDH. Mean injection times were 6 (4-18). AEs were all grade 1/2, pyrexia 84.2%, fatigue 31.6%, injection site pain 26.3%, nausea/vomiting 21.0%, hepatotoxicity 21.0%, leucopenia 10.5%. 12 patients were evaluable till Jan 2017 with median follow-up time of 6.0 months. ORR was 8.3% (1 PR), DCR 41.7% (1 PR, 4 SD) with a time to response 8-16 wks, median PFS was 13.3 wks (95%CI 8.3-18.4), OS not reached.

Conclusions

This is the first trial for evaluating intralesional oncolytic virus injection into liver metastases among melanoma pts- It is tolerable with a potentially beneficial effect. Phase 2 and combination trials are pending.

Clinical trial identification

NCT03048253.

Legal entity responsible for the study

Peking University Cancer Hospital & Institute

Funding

OrienGene Biotechnology Ltd

Disclosure

All authors have declared no conflicts of interest.

Background

Uveal melanoma is a distinct subtype of melanoma. Several previously reported studies showed that anti-PD-1 or PD-L1 antibodies, which are efficacious for cutaneous melanoma with tolerable toxicities, had only limited activities on metastatic uveal melanoma. However, since most of the patients in those studies were previously treated with ipilimumab, the efficacy of anti-PD-1 antibody when it is used prior to ipilimumab for metastatic uveal melanoma is less clear.

Methods

To evaluate the efficacy of nivolumab for Asian patients with metastatic uveal melanoma previously untreated with ipilimumab, we carried out a retrospective study using a database of National Cancer Center Hospital, Tokyo, Japan, in which nivolumab was approved one year earlier than ipilimumab. As clinical efficacy outcomes, best overall response which was evaluated by RECIST 1.1, progression-free survival (PFS), and overall survival (OS) were determined.

Results

We identified 14 patients with metastatic uveal melanoma who received nivolumab at a dosage of 3mg/kg every 2 weeks or 2mg/kg every 3 weeks. Median age was 59.5 (range, 42 - 74), and 11 patients were male. Performance status was 0 in 9 patients and 1 in 5 patients. All the patients had liver metastases and 9 patients had additional extrahepatic metastases. At baseline, serum lactate dehydrogenase (LDH) was elevated in 8 patients. Although 8 patients had previous treatment history of transarterial chemoembolization (TACE), none of the 14 patients had received any prior systemic therapies including ipilimumab. Of 12 evaluable patients, objective tumor response was observed in 1 patient for an overall response rate of 8.3%, and stable disease was observed in 5 patients. The median PFS was 10 weeks (range, 4 – 94 weeks), and the median OS was 58 weeks (range, 5 – 105 weeks).

Conclusions

Even though nivolumab is used prior to ipilimumab, metastatic uveal melanoma seems to be still refractory to nivolumab monotherapy. However, since one patient in our cohort achieved objective response, treatment strategies in combination with anti-PD1 antibody should be further investigated.

Legal entity responsible for the study

National Cancer Center Hospital

Funding

Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED, 17ck0106352h0001) and the National Cancer Center Research and Development Fund (29-A-3).

Disclosure

K. Namikawa: Honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Novartis Pharmaceutical, Toray industries, and Chugai Pharmaceutical, outside the submitted work. N. Motoi: Honoraria from Agilent Technologies, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Leica Microsystems, MSD, Novartis Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, and SRL, outside the submitted work. N. Yamazaki: Research grant and honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Novartis Pharma, and MSD.

All other authors have declared no conflicts of interest.

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.