Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma Journal Article
| Authors: | Halwani, A. S.; Panizo, C.; Isufi, I.; Herrera, A. F.; Okada, C. Y.; Cull, E. H.; Kis, B.; Chaves, J. M.; Bartlett, N. L.; Ai, W.; De La Cruz-Merino, L.; Bryan, L. J.; Houot, R.; Linton, K.; Briones, J.; Chau, I.; von Keudell, G. R.; Lu, H.; Yakovich, A.; Chen, M.; Ter Meulen, J. H.; Yurasov, S.; Hsu, F. J.; Flowers, C. R. |
| Article Title: | Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma |
| 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 mu g/dose, or 20 mu g/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 mu g/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 mu g (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: | rituximab; immunotherapy; microenvironment; follicular lymphoma; therapy; cells; hodgkin; idiotype vaccines; pembrolizumab; pd-1 blockade; tlr4; immune-checkpoint blockade; glucopyranosyl lipid a |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 63 |
| Issue: | 4 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2022-01-01 |
| Start Page: | 821 |
| End Page: | 833 |
| Language: | English |
| ACCESSION: | WOS:000727090800001 |
| DOI: | 10.1080/10428194.2021.2010057 |
| PROVIDER: | wos |
| PUBMED: | 34865586 |
| Notes: | Article -- Source: Wos |
