Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor Regression in Patients with Merkel Cell Carcinoma

Clin Cancer Res. 2019 Feb 15;25(4):1185-1195. doi: 10.1158/1078-0432.CCR-18-0469. Epub 2018 Aug 9.


Purpose: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive antitumor 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).

Patients and methods: Patients with locoregional 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 proinflammatory 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 1 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 antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.See related commentary by Marquez-Rodas et al., p. 1127.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cancer Vaccines / administration & dosage
  • Carcinoma, Merkel Cell / drug therapy*
  • Carcinoma, Merkel Cell / genetics
  • Carcinoma, Merkel Cell / immunology
  • Carcinoma, Merkel Cell / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunotherapy*
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology
  • Lipid A / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Pilot Projects
  • Toll-Like Receptor 4 / agonists*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Tumor Microenvironment / drug effects


  • Cancer Vaccines
  • Lipid A
  • TLR4 agonist G100
  • TLR4 protein, human
  • Toll-Like Receptor 4