{"doi":"10.1136/jitc-2024-010013","title":"Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors","abstract":"PURPOSE: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses. MATERIALS AND METHODS: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results. RESULTS: 36 patients were enrolled, with breast (31%), colorectal (17%), and head and neck (14%) being the more commonly enrolled cancers. Most patients (58%) had received prior immunotherapy. Therapy was well-tolerated, with G1-G2 fever (70%), neutrophilia (36%), and leukocytosis (33%) being the most common treatment-related adverse events with one case of G4 interstitial nephritis and one case of G3 hepatotoxicity and G3 colitis. Intratumoral BMS-986299 monotherapy resulted in dose-dependent increases in systemic exposure with increase in tumor CTLs (67%), CD4+ TILs (63%), along with notable above twofold increases in serum IL-1B, G-CSF and IL-6 at doses above 2000 µg. Systemic BMS-986299 exposure was positively associated with systemic cytokine elevation for G-CSF and IL-6. No antitumor activity was noted in BMS-986299 monotherapy cohort. However, in the combination therapy cohort (BMS-986299+nivolumab+ipilimumab), overall objective response rate was 10%, with confirmed PRs observed in TNBC, hormone receptor-positive, human epidermal growth factor receptor 2 negative breast cancer, and cutaneous squamous cell carcinoma. CONCLUSION: BMS-986299 in combination with immune checkpoint inhibitors demonstrated manageable toxicities, good tolerability, and promising antitumor activity in certain cancer types. TRIAL REGISTRATION NUMBER: NCT03444753.","journal":"Journal for ImmunoTherapy of Cancer","year":2025,"id":510136,"datarank":0.61683063593493,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.1465065035455575,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.1465065035455575,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":21,"citers_with_citation_signal":10,"citers_with_endowment":10,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03444753"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":340167,"name":"Shaun O’Brien","orcid":"0000-0001-5039-7470","position":1,"is_corresponding":false},{"id":407607,"name":"Rahul A. Sheth","orcid":"0000-0001-9615-8985","position":2,"is_corresponding":false},{"id":107725,"name":"David S. Hong","orcid":"0000-0001-8721-1609","position":3,"is_corresponding":false},{"id":266105,"name":"Aung Naing","orcid":"0000-0002-4803-8513","position":4,"is_corresponding":false},{"id":613748,"name":"Xiao–Ping Zhang","orcid":"0000-0001-5241-0069","position":5,"is_corresponding":false},{"id":278265,"name":"Amy Xu","orcid":"0000-0001-9650-9458","position":6,"is_corresponding":false},{"id":1365455,"name":"Lora Hamuro","orcid":"0000-0003-2367-1926","position":7,"is_corresponding":false},{"id":1366185,"name":"Rasika Suryawanshi","orcid":null,"position":8,"is_corresponding":false},{"id":1366186,"name":"D. J. McKinley","orcid":null,"position":9,"is_corresponding":false},{"id":313093,"name":"Ruslan D. Novosiadly","orcid":null,"position":10,"is_corresponding":false},{"id":258839,"name":"Sarina A. Piha‐Paul","orcid":"0000-0001-9455-1660","position":11,"is_corresponding":false},{"id":1025082,"name":"Blessie Elizabeth Nelson","orcid":"0000-0002-8227-638X","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"39824531","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}