PURPOSE:
G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC).
EXPERIMENTAL DESIGN:
Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy.
RESULTS:
IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+and CD4+T cells and activation of immune-related genes. These pro-inflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 Cohort A patients successfully completed therapy; 2 patients remain recurrence-free at 44+ and 41+ months, including one with a pathologic complete response after G100 alone. In Cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy.
CONCLUSIONS:
In this first-in-human study, IT G100 induced anti-tumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.