Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma. Issue 4 (21st March 2022)

• Record Type: Journal Article
• Authors: Halwani, Ahmad S.; Panizo, Carlos; Isufi, Iris; Herrera, Alex F.; Okada, Craig Y.; Cull, Elizabeth H.; Kis, Bela; Chaves, Jorge M.; Bartlett, Nancy L.; Ai, Weiyun; de la Cruz-Merino, Luis; Bryan, Locke J.; Houot, Roch; Linton, Kim; Briones, Javier; Chau, Ian; von Keudell, Gottfried R.; Lu, Hailing; Yakovich, Adam; Chen, Michael; Meulen JH, ter; Yurasov, Sergey; Hsu, Frank J.; Flowers, Christopher R.
• Is Part Of: Leukemia & lymphoma. Volume 63:Issue 4(2022)
• Page Start: 821
• Page End: 833
• Publication Date: 2022-03-21
• Subjects: TLR4 -- glucopyranosyl lipid A -- follicular lymphoma -- immunotherapy -- pembrolizumab; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2021.2010057
• Languages: English
• ISSNs: 1042-8194

Abstract

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.