Pilot Study of Toll-Like Receptor 4 Agonist in Merkel Cell Carcinoma
Posted: Thursday, January 10, 2019
Research published in Clinical Cancer Research found that intratumoral administration of G100 (IT G100), a Toll-like receptor 4 (TLR4) agonist, may prove to be of benefit for patients with Merkel cell carcinoma. G100 has been shown in preclinical models to encourage antitumor responses.
“In this first-in-human study, IT G100 induced antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity,” concluded Shailender Bhatia, MD, of the University of Washington Medical Center, and colleagues.
The study included two arms. Cohort A (3 patients with locoregional Merkel cell carcinoma) received neoadjuvant IT G100 twice weekly at 5 μg per dose, followed by surgery and radiation therapy. Cohort B (7 patients with metastatic Merkel cell carcinoma) were treated with 3 doses of IT G100 in a 6-week cycle, with the option of additional cycles with or without radiation therapy.
IT G100 appeared to encourage systemic immunity through increased inflammation in the targeted tumors, which was associated with tumor regression. The majority of adverse events related to treatment were grade 1 or grade 2 reactions at the site of injection.
All 3 patients in cohort A completed the study; 2 of them remain recurrence-free at 44+ and 41+ months, respectively, with 1 patient achieving a complete pathologic response after IT G100 treatment alone. Of the 7 patients in cohort B, 2 achieved a sustained partial response lasting at least 33 months after 2 cycles of IT G100 therapy.
“The data suggest IT G100 to be a promising agent for further investigation in cancer therapy, either as a monotherapy or in combination with other immunotherapies,” the investigator concluded.
Disclosure: The study authors’ disclosure information can be found at aacrjournals.org.