Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma

Leuk Lymphoma. 2022 Apr;63(4):821-833. doi: 10.1080/10428194.2021.2010057. Epub 2021 Dec 6.

Abstract

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Keywords: TLR4; follicular lymphoma; glucopyranosyl lipid A; immunotherapy; pembrolizumab.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Humans
  • Lymphoma, Follicular* / drug therapy
  • Toll-Like Receptor 4* / agonists

Substances

  • Antibodies, Monoclonal, Humanized
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT02501473