{"doi":"10.3390/cancers16010091","title":"First-in-Human Dose-Escalation Study of the Novel Oral Depsipeptide Class I-Targeting HDAC Inhibitor Bocodepsin (OKI-179) in Patients with Advanced Solid Tumors","abstract":"(1) Background: Histone deacetylases (HDACs) play a critical role in epigenetic signaling in cancer; however, available HDAC inhibitors have limited therapeutic windows and suboptimal pharmacokinetics (PK). This first-in-human phase I dose escalation study evaluated the safety, PK, pharmacodynamics (PDx), and efficacy of the oral Class I-targeting HDAC inhibitor bocodepsin (OKI-179). (2) Patients and Methods: Patients (n = 34) with advanced solid tumors were treated with OKI-179 orally once daily in three schedules: 4 days on 3 days off (4:3), 5 days on 2 days off (5:2), or continuous in 21-day cycles until disease progression or unacceptable toxicity. Single-patient escalation cohorts followed a standard 3 + 3 design. (3) Results: The mean duration of treatment was 81.2 (range 11–447) days. The most frequent adverse events in all patients were nausea (70.6%), fatigue (47.1%), and thrombocytopenia (41.2%). The maximum tolerated dose (MTD) of OKI-179 was 450 mg with 4:3 and 200 mg with continuous dosing. Dose-limiting toxicities included decreased platelet count and nausea. Prolonged disease control was observed, including two patients with platinum-resistant ovarian cancer. Systemic exposure to the active metabolite exceeded the preclinical efficacy threshold at doses lower than the MTD and was temporally associated with increased histone acetylation in circulating T cells. (4) Conclusions: OKI-179 has a manageable safety profile at the recommended phase 2 dose (RP2D) of 300 mg daily on a 4:3 schedule with prophylactic oral antiemetics. OKI-179 is currently being investigated with the MEK inhibitor binimetinib in patients with NRAS-mutated melanoma in the phase 2 Nautilus trial.","journal":"Cancers","year":2023,"id":348939,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9451,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":533395,"name":"Jodi Kagihara","orcid":"0000-0001-8379-961X","position":1,"is_corresponding":false},{"id":311499,"name":"Bradley R. Corr","orcid":"0000-0002-6608-2585","position":2,"is_corresponding":false},{"id":559293,"name":"S. Lindsey Davis","orcid":"0000-0003-3899-9481","position":3,"is_corresponding":false},{"id":332486,"name":"Christopher H. Lieu","orcid":"0000-0002-4852-4642","position":4,"is_corresponding":false},{"id":1091692,"name":"Sunnie S. Kim","orcid":"0009-0008-3871-5112","position":5,"is_corresponding":false},{"id":28359,"name":"Antonio Jimeno","orcid":"0000-0001-8560-0440","position":6,"is_corresponding":false},{"id":230277,"name":"D. Ross Camidge","orcid":"0000-0003-3430-3213","position":7,"is_corresponding":false},{"id":1092166,"name":"Jud Williams","orcid":null,"position":8,"is_corresponding":false},{"id":1092167,"name":"Amy M. Heim","orcid":null,"position":9,"is_corresponding":false},{"id":559969,"name":"Anne C. Martin","orcid":null,"position":10,"is_corresponding":false},{"id":677413,"name":"John A. DeMattei","orcid":null,"position":11,"is_corresponding":false},{"id":1091693,"name":"Nisha Holay","orcid":"0000-0003-4363-3521","position":12,"is_corresponding":false},{"id":582272,"name":"Todd Triplett","orcid":"0000-0001-5494-6510","position":13,"is_corresponding":false},{"id":291191,"name":"Sabine Eckhardt","orcid":"0000-0001-6958-5375","position":14,"is_corresponding":false},{"id":1029420,"name":"Kevin Litwiler","orcid":"0009-0009-2220-4024","position":15,"is_corresponding":false},{"id":96888,"name":"James D. Winkler","orcid":null,"position":16,"is_corresponding":false},{"id":676495,"name":"Anthony D. Piscopio","orcid":"0009-0004-3611-463X","position":17,"is_corresponding":false},{"id":260393,"name":"Jennifer R. Diamond","orcid":"0000-0002-0703-2772","position":18,"is_corresponding":false},{"id":436508,"name":"Anna Schreiber","orcid":"0000-0003-2136-2476","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:12:10.335697Z","pmid":"38201519","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":[]}