SITC 2019: Adenovirus Plus Pembrolizumab in Resistant Melanoma
Posted: Wednesday, November 20, 2019
The engineered adenovirus ONCOS-102, when used in combination with pembrolizumab, seems to induce both systemic and local immune activation that may produce objective responses in patients with melanoma that is refractory to anti–PD-1 therapy. Alexander Shoushtari, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues presented the findings of this pilot study at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland (Abstract O20).
In total, nine patients who had advanced or unresectable melanoma that had progressed after PD-1 blockade were enrolled in the study. Patients received three injections of ONCOS-102 with 3 x 1011 viral particles directly into their tumor on days 1, 4, and 8, followed by pembrolizumab. Biopsies of tumors were taken at baseline and then again at weeks 3 and 9.
Confirmed responses were seen in three of nine patients, with one complete response and two partial responses reported. The clinical benefit rate—defined as a partial response, complete response, or stable disease—was 33%. All patients showed evidence of innate immune activation, defined as a greater than twofold increase in proinflammatory cytokines and circulating CD8 and PD-1/CD8 T cells. Infiltration of CD8 T cells into tumors was seen in seven patients who had paired tumor biopsies, and six of these seven patients had PD-1/CD8 T-cell infiltration into their tumors.
Common adverse events included chills and fever, which were associated with adenovirus replication. However, no dose-limiting toxicities were reported. There were five serious adverse events seen in three different patients, including one patient who had infectious colitis that was related to ONCOS-102.
Disclosure: For full disclosures of other study authors, visit sitcancer.org.