Daiichi Sankyo closes enrollment on valemetostat-ADC combo trial at 98 patients
The Phase 1 study pairs an EZH1/EZH2 inhibitor with Daiichi's DXd antibody-drug conjugates in breast, gastric and lung cancers, with dose-finding data still to come.
Executive Summary
- Daiichi Sankyo's Phase 1 study testing valemetostat tosylate alongside its DXd antibody-drug conjugates closed enrollment and shifted to Active, not recruiting, moving the trial from patient intake into its dose-finding and expansion analysis.
- The study is built to answer a tolerability question first: whether adding an EZH1/EZH2 inhibitor on top of an ADC backbone is safe enough to carry into an expansion cohort that will then test tumor response.
- The combination sits inside a landscape of ADC-heavy breast cancer programs that share Daiichi's DXd targets but not its dual epigenetic-inhibitor addition, leaving this as one of a small number of active studies pairing an EZH1/EZH2 inhibitor with an approved ADC class.
- Enrollment completion advances the trial toward its dose-finding readout without yet establishing whether the combination clears the bar of added benefit over the ADC components alone.
The status change
The trial, registered as NCT06244485, updated its status from Recruiting to Active, not recruiting and recorded final enrollment of 98 patients, down from a 210-patient figure the registry had carried since June 2024. The study tests valemetostat tosylate, an EZH1/EZH2 dual inhibitor also known as DS-3201b, combined with Daiichi's DXd-class antibody-drug conjugates including trastuzumab deruxtecan (Enhertu), across sub-protocols in HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer. NCT06244485A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid TumorsNCT06244485
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial tests
The Phase 1 design runs in two parts: a dose-escalation phase measuring dose-limiting toxicities and treatment-emergent adverse events, followed by a dose-expansion phase measuring objective response rate by investigator assessment under RECIST v1.1. Secondary endpoints include duration of response, progression-free survival and overall survival, tracked out to roughly five years. Because the primary measures in Part 1 are safety and dose-finding, the immediate information value of the trial is whether the combination is tolerable enough to carry a recommended dose into expansion, not yet whether it works. NCT06244485A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid TumorsNCT06244485
Enrollment and timing
The trial opened in February 2024, targeted 140 patients at first submission, and expanded that target to 210 in June 2024 before settling at a final enrolled count of 98. The primary completion date has held at November 1, 2028, since an April 2024 amendment moved it in from February 2029, and the sponsor has not changed it since. Eligibility criteria were amended twice over the trial's life, changes consistent with the sub-protocol structure of a multi-cohort dose-finding study rather than a shift in what the trial is testing. NCT06244485A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid TumorsNCT06244485
Where it sits competitively
Valemetostat's target, EZH1, appears in only two active industry trials in breast cancer, with Daiichi's own program as one of them, while eighteen sibling-target trials work adjacent epigenetic or ADC mechanisms in the same indication family. The nearest direct comparator by target and indication is Merck's sacituzumab tirumotecan, a Phase 3 antibody-drug conjugate in breast cancer that, like several other named comparators, including AstraZeneca's trastuzumab deruxtecan and Gilead's sacituzumab govitecan, shares Daiichi's ADC target space but not its EZH1/EZH2 addition. Those Phase 3 programs are testing ADCs largely as monotherapy or against chemotherapy; this trial is testing whether stacking an epigenetic inhibitor on top of an ADC backbone adds benefit without adding toxicity that erodes the combination's tolerability. NCT06244485A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid TumorsNCT06244485
Sponsor track record
Daiichi Sankyo has completed 82% of its Breast Cancer trials across 11 studies and holds an 88% completion rate across 310 trials globally, context for reading a Phase 1 study that is non-registrational and still short of its dose-finding readout.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.