Investigational Drug
Valemetostat
TrialFetch AI Analysis
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Overview
Valemetostat is an oral cancer drug under investigation for several malignancies. It is approved in Japan for relapsed or refractory adult T-cell leukemia/lymphoma (ATL) and peripheral T-cell lymphoma (PTCL); its use in other settings remains investigational. The main published efficacy results come from single-arm phase 2 trials, so they do not establish how it compares with other treatments. (pubmed.ncbi.nlm.nih.gov)
Mechanism of action
Valemetostat inhibits EZH1 and EZH2, enzymes in the PRC2 complex that help silence genes by adding methyl groups to histone H3. Blocking both enzymes reduces this gene-silencing mark. Research in ATL has also identified mechanisms by which tumors can develop resistance. (pmc.ncbi.nlm.nih.gov)
Efficacy
- ATL: In a Japanese phase 2 trial of 25 previously treated patients, 12 responded (48%): five had complete and seven had partial remissions. Median response duration had not been reached at a median follow-up of 6.5 months. (pmc.ncbi.nlm.nih.gov)
- PTCL: In the phase 2 VALENTINE-PTCL01 trial, 52 of 119 efficacy-evaluable patients responded (43.7%), including 17 complete responses (14.3%). Median response duration was 11.9 months. (pmc.ncbi.nlm.nih.gov)
Safety
Low blood counts were prominent. In VALENTINE-PTCL01, the most common grade 3–4 adverse events among 133 patients with PTCL were thrombocytopenia (23%), anemia (19%), and neutropenia (17%). The smaller ATL phase 2 trial also reported these and other blood-count abnormalities; two of its 25 patients stopped treatment because of adverse events. (pubmed.ncbi.nlm.nih.gov)
Further reading
- ATL phase 2 trial (Blood)
- VALENTINE-PTCL01 phase 2 trial (The Lancet Oncology)
- Mechanism and resistance study (Nature)
Last updated: Sep 2026
Active trials using Valemetostat
Found 3 active trials using this drug:
TrialFetch AI summary: This single-arm study enrolls men with progressive metastatic castration-resistant prostate adenocarcinoma previously treated with an androgen receptor pathway inhibitor who remain on androgen deprivation therapy. Participants receive darolutamide plus investigational valemetostat, an EZH1/EZH2 inhibitor that blocks PRC2-mediated histone methylation.
ClinicalTrials.gov ID: NCT07244341
TrialFetch AI summary: For adults with unresectable locally advanced or metastatic HCC who have not received systemic therapy for advanced disease and have Child–Pugh A liver function and ECOG 0–1, this study adds oral valemetostat to first-line atezolizumab and bevacizumab. Valemetostat is an investigational EZH1/EZH2 histone methyltransferase inhibitor.
ClinicalTrials.gov ID: NCT06294548
TrialFetch AI summary: Adults with extensive-stage small cell lung cancer, ECOG 0–1, and stable disease or a response after four cycles of first-line platinum-doublet chemotherapy plus atezolizumab receive maintenance valemetostat, an EZH1/2 inhibitor, with continued atezolizumab.
ClinicalTrials.gov ID: NCT06807632
