LAUSR

Background Melanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse prognosis. Hence, there is an urgent need for improved treatment for melanoma in Asians. This phase Ib trial evaluated the safety and efficacy of the modified herpes simplex virus-1 oncolytic virus OrienX010 in Chinese patients with unresectable stage IIIC–IV melanoma. Methods Patients were treated in two different cohorts. In cohort 08 (n=12), patients received up to 5 mL of 8×107 pfu/mL OrienX010 intratumoral injections every 2 weeks until disease progression and responses were evaluated every 6 weeks. In cohort 09 (n=14), patients received up to 10 mL of 8×107 pfu/mL OrienX010 intratumoral injections and responses were evaluated every 8 weeks. Results Between June 2014 and May 2017, 26 patients were enrolled, including 18 (69.2%) patients with acral melanoma. Fever and injection site reaction were the most frequent adverse events. Only one patient experienced a grade ≥3 adverse event and no dose-limiting toxicities were observed. The objective response rate was 19.2% and the disease control rate was 53.8%. The median duration of response was 6.0 months. Antitumor effects were observed in 54.6% of injected lesions and 48.8% of non-injected lesions, including one (16.7%) of six evaluable distant lung metastases. The median progression-free survival was 2.9 months and overall survival was 19.2 months. Compared with patients treated in cohort 08, patients treated in cohort 09 had an improved objective response rate (28.6% vs 8.3%) and a median progression-free survival of 3.0 months vs 2.8 months. Conclusions OrienX010 oncolytic virotherapy has a tolerable safety profile with antitumor effects in both injected and non-injected metastases and warrants further evaluation in patients with melanoma. Based on these results, the higher cohort 09 dose (up to 10 mL of 8×107 pfu/mL every 2 weeks) was selected as the recommended phase II dose for ongoing trials. Trial registration number CTR20140631 (cohort 08), CTR20150881 (cohort 09).