Pilot Study of Intratumoral G100 in Merkel Cell Carcinoma
Multiple recent reports have addressed the activity of programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab and avelumab, in Merkel cell carcinoma. However, approximately half of all patients who receive these agents do not maintain a persistent response. In an effort to overcome the immunosuppressive mechanisms of the disease, researchers investigated the intratumoral administration of G100, a synthetic Toll-like receptor 4 agonist. Findings from the small pilot study were published by Bhatia et al in Clinical Cancer Research.
In the study, 3 patients with locoregional Merkel cell carcinoma were assigned to receive neoadjuvant G100 twice weekly at 5 μg per dose, followed by surgery and radiotherapy. In addition, 7 patients with metastatic Merkel cell carcinoma were assigned to receive 3 doses of G100 in a 6-week cycle and could receive an additional cycle with or without radiotherapy. The study aimed to assess the safety, efficacy, and immunologic activity of intratumoral G100.
Study Findings
Intratumoral G100 led to increased inflammation in injected Merkel cell carcinoma tumors with infiltration of CD8 and CD4 T cells and activation of immune-related genes, and these were associated with local tumor regression.
All 3 patients with locoregional disease successfully completed therapy; 2 patients remain recurrence-free at 44+ and 41+ months, including 1 with a pathologic complete response after G100 alone. Among the 7 patients with metastatic disease, 2 achieved sustained partial responses, both lasting at least 33 months after 2 cycles of therapy. Treatment-related adverse events were mostly injection-site reactions (grade 1 or 2).
The study authors concluded, “In this first-in-human study, [intratumoral] G100 induced antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.”
Disclosure: The study authors’ full disclosures can be found at clincancerres.aacrjournals.org.
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