{"doi":"10.1093/oncolo/oyaf169","title":"Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors","abstract":"BACKGROUND: This was a first-in-human, phase I, dose-escalation study evaluating the safety, pharmacokinetics, and preliminary efficacy of zavondemstat (TACH101), an epigenetic targeting inhibitor of KDM4 histone demethylase, in patients with heavily pre-treated advanced/metastatic cancers. PATIENTS AND METHODS: Patients received zavondemstat orally on a weekly schedule in 28-day cycles. Dose escalation followed a Bayesian optimal interval design and explored both intermittent and continuous dosing. The primary objectives were to assess safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary objectives included pharmacokinetics and radiographic response per Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Thirty patients were enrolled across 6 dose cohorts. MTD was not reached at the maximum dose tested. The most common treatment-related adverse events (TRAEs) were diarrhea (12%), fatigue (7%), decreased appetite (7%), nausea (7%), and hyponatremia (7%). All TRAEs were grade 1 or 2. No serious TRAEs or DLTs were reported. Of 23 response-evaluable patients, 10 (44%) achieved stable disease (SD). Two patients (9%) had SD ≥ 6 months, including a patient with castration-resistant prostate cancer and a patient with leiomyosarcoma. A third patient (leiomyosarcoma) receiving ongoing treatment with zavondemstat under compassionate use has had SD for 6+ months. Zavondemstat demonstrated a dose-proportional exposure profile with a half-life of about 1.5 hours. There was no to minimal drug accumulation observed. CONCLUSIONS: Zavondemstat was very well tolerated and showed encouraging preliminary clinical benefit in heavily pretreated patients with advanced cancer. Continued evaluation of zavondemstat is warranted.","journal":"The Oncologist","year":2025,"id":523729,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8771,"is_data_producer":false,"deposit_databanks":null,"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":531649,"name":"Farshid Dayyani","orcid":"0000-0002-4970-5189","position":1,"is_corresponding":false},{"id":1396637,"name":"David Sommerhalder","orcid":"0000-0002-7033-9064","position":2,"is_corresponding":false},{"id":1397117,"name":"Andrae Lavon Vandross","orcid":null,"position":3,"is_corresponding":false},{"id":1201744,"name":"Meredith S. Pelster","orcid":null,"position":4,"is_corresponding":false},{"id":1221479,"name":"Jason T. Henry","orcid":"0000-0003-1991-4227","position":5,"is_corresponding":false},{"id":1396638,"name":"Cesar A. Perez","orcid":"0000-0001-5860-4921","position":6,"is_corresponding":false},{"id":411362,"name":"Abhijit Chakraborty","orcid":"0000-0002-3822-5657","position":7,"is_corresponding":false},{"id":1022921,"name":"Mehmet A. Baysal","orcid":"0000-0002-8446-6531","position":8,"is_corresponding":false},{"id":1397118,"name":"Chandtip Chandhasin","orcid":null,"position":9,"is_corresponding":false},{"id":1397119,"name":"Yiyun Dai","orcid":null,"position":10,"is_corresponding":false},{"id":1397120,"name":"S. Tu","orcid":null,"position":11,"is_corresponding":false},{"id":1397121,"name":"Ivan King","orcid":null,"position":12,"is_corresponding":false},{"id":1397122,"name":"Frank Perabo","orcid":null,"position":13,"is_corresponding":false},{"id":108756,"name":"Apostolia M. Tsimberidou","orcid":"0000-0003-2713-233X","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40580997","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":[]}