{"doi":"10.1038/s41375-021-01328-9","title":"Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms","abstract":"We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.","journal":"Leukemia","year":2021,"id":146981,"datarank":0.7830533737617489,"base_score":5.220355825078325,"endowment":5.220355825078325,"self_citation_contribution":0.7830533737617489,"citation_network_contribution":0.0,"self_endowment_contribution":0.7830533737617489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":184,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9189,"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":233365,"name":"Martin Wermke","orcid":"0000-0002-4844-4087","position":1,"is_corresponding":false},{"id":108819,"name":"Virginia M. Klimek","orcid":null,"position":2,"is_corresponding":false},{"id":36436,"name":"Peter L. Greenberg","orcid":"0000-0002-7615-9443","position":3,"is_corresponding":false},{"id":625317,"name":"Patricia Font","orcid":"0000-0002-9738-4930","position":4,"is_corresponding":false},{"id":284121,"name":"Rami S. Komrokji","orcid":"0000-0002-1876-5269","position":5,"is_corresponding":false},{"id":350221,"name":"Jay Yang","orcid":"0000-0003-0790-7951","position":6,"is_corresponding":false},{"id":579654,"name":"Andrew M. Brunner","orcid":"0000-0002-2169-4115","position":7,"is_corresponding":false},{"id":278921,"name":"Hetty E. Carraway","orcid":"0000-0001-5241-3614","position":8,"is_corresponding":false},{"id":625318,"name":"Lionel Adès","orcid":"0000-0002-9020-8766","position":9,"is_corresponding":false},{"id":284256,"name":"Aref Al‐Kali","orcid":"0000-0002-0824-3715","position":10,"is_corresponding":false},{"id":625319,"name":"Juan Manuel Alonso‐Domínguez","orcid":"0000-0001-6233-5912","position":11,"is_corresponding":false},{"id":625320,"name":"Ana Alfonso Piérola","orcid":"0000-0002-2478-5354","position":12,"is_corresponding":false},{"id":108792,"name":"Catherine C. Coombs","orcid":"0000-0003-4656-7304","position":13,"is_corresponding":false},{"id":56441,"name":"H. Joachim Deeg","orcid":"0000-0002-4426-9023","position":14,"is_corresponding":false},{"id":11109,"name":"Ian W. Flinn","orcid":"0000-0001-6724-290X","position":15,"is_corresponding":false},{"id":339782,"name":"James M. Foran","orcid":"0000-0003-1673-1708","position":16,"is_corresponding":false},{"id":230408,"name":"Guillermo Garcia‐Manero","orcid":"0000-0002-3631-2482","position":17,"is_corresponding":false},{"id":394293,"name":"Michael B. Maris","orcid":null,"position":18,"is_corresponding":false},{"id":626766,"name":"Malgorzata McMasters","orcid":null,"position":19,"is_corresponding":false},{"id":318323,"name":"Jean‐Baptiste Micol","orcid":"0000-0003-0934-294X","position":20,"is_corresponding":false},{"id":625321,"name":"Jaime Pérez de Oteyza","orcid":"0000-0002-8338-2037","position":21,"is_corresponding":false},{"id":50605,"name":"Felicitas Thol","orcid":"0000-0001-5848-6152","position":22,"is_corresponding":false},{"id":284267,"name":"Eunice S. Wang","orcid":"0000-0002-8644-0968","position":23,"is_corresponding":false},{"id":309199,"name":"Justin M. Watts","orcid":"0000-0001-5213-5482","position":24,"is_corresponding":false},{"id":309200,"name":"Justin Taylor","orcid":"0000-0003-4407-6325","position":25,"is_corresponding":false},{"id":34476,"name":"Richard M. Stone","orcid":"0000-0002-7526-2633","position":26,"is_corresponding":false},{"id":626767,"name":"Vikram Gourineni","orcid":null,"position":27,"is_corresponding":false},{"id":626768,"name":"Alyssa J. Marino","orcid":null,"position":28,"is_corresponding":false},{"id":626769,"name":"Huilan Yao","orcid":null,"position":29,"is_corresponding":false},{"id":626770,"name":"Benoit Destenaves","orcid":null,"position":30,"is_corresponding":false},{"id":625322,"name":"Xiaobin Yuan","orcid":"0000-0002-0497-430X","position":31,"is_corresponding":false},{"id":625323,"name":"Kun Yu","orcid":"0000-0002-8838-3039","position":32,"is_corresponding":false},{"id":626771,"name":"Sara Dar","orcid":null,"position":33,"is_corresponding":false},{"id":626772,"name":"Lernik Ohanjanian","orcid":null,"position":34,"is_corresponding":false},{"id":626773,"name":"Keisuke Kuida","orcid":null,"position":35,"is_corresponding":false},{"id":625324,"name":"Jianjun Xiao","orcid":"0000-0002-8469-6134","position":36,"is_corresponding":false},{"id":626774,"name":"Catherine Scholz","orcid":null,"position":37,"is_corresponding":false},{"id":273868,"name":"Antonio Gualberto","orcid":"0000-0002-6590-839X","position":38,"is_corresponding":false},{"id":284265,"name":"Uwe Platzbecker","orcid":"0000-0003-1863-3239","position":39,"is_corresponding":false},{"id":34477,"name":"David P. Steensma","orcid":"0000-0001-5130-9284","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:30.206628Z","pmid":"34172893","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":[]}