Phase 1 study of BMS-986299 as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors

Resistance to immune checkpoint inhibitors poses a significant challenge in cancer treatment, particularly in tumors with limited T-cell infiltration. BMS-986299 is a first-in-class NLRP3 agonist, which can promote T-cell infiltration into the tumor microenvironment. A phase 1 study at MD Anderson Cancer Center (Houston, TX) evaluated intratumoral BMS-986299 as monotherapy and in combination with intraveneous nivolumab and ipilimumab in patients with advanced solid tumors. BMS-986299 was well-tolerated, with only one grade 4 and two grade 3 adverse events among 36 patients. No antitumor activity was noted in the BMS-986299 monotherapy cohort, but in the combination therapy cohort the overall response rate was 10%, with confirmed partial responses observed in triple negative breast cancer, HR+ HER2- breast cancer, and cutaneous squamous cell carcinoma.The authors conclude that BMS-986299 in combination with nivolumab and ipilimumab demonstrated manageable toxicities, good tolerability, and promising antitumor activity in patiënts with certain cancer types.