Immunotherapy Combination Promising in Advanced Melanoma

Brendan D. Curti, MD

Combination treatment with an intratumoral injection of Coxsackievirus A21 (CVA21) and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab has demonstrated durable response with minimal toxicity among patients with advanced melanoma, according to data (abstract CT114) presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, held April 1–5 in Washington, DC.

Response to the combination occurred even among several patients whose melanoma had progressed despite prior treatment with an immune checkpoint inhibitor.

“We are excited that the ipilimumab–CVA21 combination has yielded responses greater than 6 months for a number of patients, both those whose melanoma has progressed after immune checkpoint inhibitor therapy and those who have not yet been treated with these immunotherapeutics,” said Brendan D. Curti, MD, director of the clinical biotherapy program and co-director of the melanoma program at the Earle A. Chiles Research Institute of Providence Cancer Center in Portland, Oregon, in a press release. “Based on these promising preliminary data and the urgent need for new treatments for advanced melanoma patients refractory to immune checkpoint inhibitors, we are expanding the trial up to 70 patients.”

CVA21 is a bioselected, nongenetically altered common cold RNA virus. According to Curti, it can directly infect many different cancer cells and as such it can boost adaptive and innate anticancer immune responses. Prior data from a phase II study of CVA21 showed that intratumoral injection of advanced melanoma lesions increased tumor immune cell infiltration, as well as upregulation of interferon gamma response and immune checkpoint genes, including CD122. CD122 may be a potential marker for enhanced antitumor activity by anti–CTLA-4 blockade strategies.

The data presented included 25 patients evaluable for safety and 22 patients evaluable for response. Of the first 22 patients enrolled, the overall response rate was 50%. There were four complete responses and seven partial responses. The overall response rate for immune checkpoint inhibitor–naive patients was 60%, and it was 38% among those patients with previous exposure.

The disease control rate is currently 78%. All responses were observed within 3.5 months, with complete tumor responses observed in individual injected and non-injected lesions.

To date, the combination therapy has been well tolerated, with only two grade 3 or higher treatment-related adverse events.

“While still a small dataset, we are encouraged by the low frequency of severe adverse events,” said Curti. “Historically, about 25% of patients treated with ipilimumab have treatment-related grade 3 or higher adverse events. We have seen this in just 8% of patients treated with the combination, but we will need larger numbers of patients to confirm this finding.”