Investigational Drug
Tulmimetostat
TrialFetch AI Analysis
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Overview
Tulmimetostat (CPI-0209; DZR123) is an investigational oral cancer drug. Human results have been reported from an early-phase, single-arm study in advanced cancers, including ARID1A-mutated ovarian clear cell and endometrial carcinomas. These results establish preliminary activity, not clinical benefit compared with existing treatments. (asco.org)
Mechanism of action
Tulmimetostat inhibits EZH2 and EZH1, enzymes involved in PRC2-mediated gene repression. Laboratory studies found that it reduced the repressive histone mark H3K27me3 and inhibited growth in several ARID1A-mutant tumor models. A study of samples from treated patients also found evidence of target engagement; the laboratory findings do not, by themselves, establish efficacy in people. (pubmed.ncbi.nlm.nih.gov)
Efficacy
In a 2025 phase II dose-optimization report with an October 15, 2024 data cutoff, confirmed responses among efficacy-evaluable patients with ARID1A-mutated ovarian clear cell carcinoma were 4/20 (20%) at 200 mg, 2/20 (10%) at 300 mg, and 1/14 (7%) at 350 mg. In endometrial carcinoma, they were 0/10, 2/15 (13%), and 4/11 (36%), respectively. These are small, non-comparative groups; the percentages should not be interpreted as a reliable comparison between doses. (asco.org)
Safety
In those cohorts, dose modifications due to treatment-emergent adverse events were frequent and generally more common at higher doses. Reported grade 3 or worse treatment-related events included anemia, thrombocytopenia, neutropenia, and diarrhea. No treatment-related deaths were reported in the abstract. (asco.org)
Further reading
- 2025 ASCO phase II efficacy and safety abstract
- Peer-reviewed mechanism and target-engagement study
- Phase I/II trial description
Last updated: Sep 2026
Active trials using Tulmimetostat
Found 5 active trials using this drug:
TrialFetch AI summary: Adults with advanced NSCLC that has progressed after first- or second-line immunotherapy, including anti-PD-1/PD-L1 therapy, receive oral tulmimetostat, an investigational EZH2/EZH1 inhibitor, plus pembrolizumab (PD-1 blockade). Patients with EGFR or ALK alterations or active brain metastases are excluded.
ClinicalTrials.gov ID: NCT05467748
TrialFetch AI summary: Adult men with progressive, radiographically evident mCRPC after a second-generation androgen receptor pathway inhibitor receive oral tulmimetostat, an EZH2/EZH1 inhibitor, plus luxdegalutamide, an androgen receptor–degrading PROTAC. The combination is dose-escalated and then compared with investigator-selected standard of care; the randomized portion requires patients to be taxane-naive in the mCRPC setting.
ClinicalTrials.gov ID: NCT07206056
TrialFetch AI summary: Adult men with metastatic hormone-sensitive prostate cancer who remain on androgen-deprivation therapy receive investigational tulmimetostat, an EZH2/EZH1 inhibitor, with darolutamide or abiraterone plus prednisone during dose escalation. The randomized expansion compares tulmimetostat plus darolutamide with darolutamide alone.
ClinicalTrials.gov ID: NCT07190300
TrialFetch AI summary: Patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer receive carboplatin plus oral tulmimetostat (CPI-0209), an investigational EZH2/EZH1 inhibitor, followed by tulmimetostat maintenance. The study evaluates combination dosing and safety, with response and progression-free survival as secondary outcomes.
ClinicalTrials.gov ID: NCT05942300
TrialFetch AI summary: Adults with previously treated advanced solid tumors or lymphoma, including disease-specific cohorts defined by ARID1A mutation or BAP1 loss, receive oral tulmimetostat, an investigational EZH2/EZH1 inhibitor that disrupts PRC2-mediated gene repression. A metastatic castration-resistant prostate cancer cohort receives tulmimetostat with enzalutamide.
ClinicalTrials.gov ID: NCT04104776
