{"doi":"10.1136/jitc-2021-002371","title":"Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor","abstract":"BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. RESULTS: Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. CONCLUSIONS: Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.","journal":"Journal for ImmunoTherapy of Cancer","year":2021,"id":149944,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":99,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":637820,"name":"Yoshinobu Koguchi","orcid":"0000-0002-5733-5755","position":1,"is_corresponding":false},{"id":625194,"name":"Rom S. Leidner","orcid":"0000-0003-0788-7938","position":2,"is_corresponding":false},{"id":486128,"name":"Annah S. Rolig","orcid":"0000-0001-7080-4352","position":3,"is_corresponding":false},{"id":637821,"name":"Elizabeth R. Sturgill","orcid":"0000-0001-8921-7414","position":4,"is_corresponding":false},{"id":639265,"name":"Zhaoyu Sun","orcid":null,"position":5,"is_corresponding":false},{"id":625196,"name":"Yaping Wu","orcid":"0000-0002-5133-4698","position":6,"is_corresponding":false},{"id":387974,"name":"Venkatesh Rajamanickam","orcid":"0000-0001-6864-7589","position":7,"is_corresponding":false},{"id":69704,"name":"Brady Bernard","orcid":"0000-0003-2118-9829","position":8,"is_corresponding":false},{"id":487399,"name":"Ian Hilgart-Martiszus","orcid":null,"position":9,"is_corresponding":false},{"id":458291,"name":"Christopher Fountain","orcid":null,"position":10,"is_corresponding":false},{"id":626674,"name":"George Morris","orcid":null,"position":11,"is_corresponding":false},{"id":637822,"name":"Noriko Iwamoto","orcid":"0000-0001-5471-7363","position":12,"is_corresponding":false},{"id":637823,"name":"Takashi Shimada","orcid":"0000-0001-7182-7003","position":13,"is_corresponding":false},{"id":304083,"name":"Shu‐Ching Chang","orcid":"0000-0002-6534-0124","position":14,"is_corresponding":false},{"id":637824,"name":"Peter G. Traber","orcid":"0000-0002-5952-5720","position":15,"is_corresponding":false},{"id":639266,"name":"Eliezer Zomer","orcid":null,"position":16,"is_corresponding":false},{"id":639267,"name":"Jessie Horton","orcid":null,"position":17,"is_corresponding":false},{"id":637825,"name":"Harold Shlevin","orcid":"0000-0002-9070-1147","position":18,"is_corresponding":false},{"id":486131,"name":"William L. Redmond","orcid":"0000-0002-2572-1731","position":19,"is_corresponding":false},{"id":425698,"name":"Brendan D. Curti","orcid":"0000-0003-3948-2708","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:43:01.325389Z","pmid":"33837055","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":[]}