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

2021; Taylor & Francis; Volume: 63; Issue: 4 Linguagem: Inglês

10.1080/10428194.2021.2010057

1042-8194

Ahmad Halwani, Carlos Panizo, Iris Isufi, Alex F. Herrera, Craig Okada, Elizabeth H. Cull, Béla Kis, Jorge Chaves, Nancy L. Bartlett, Weiyun Z. Ai, Luis de la Cruz‐Merino, Locke J. Bryan, Roch Houot, Kim Linton, Javier Briones, Ian Chau, Gottfried R. von Keudell, Hailing Lu, Adam J. Yakovich, Michael Chen, ter Meulen JH, Sergey Yurasov, Frank J. Hsu, Christopher R. Flowers,

Cancer Immunotherapy and Biomarkers

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.