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Evaluating valemetostat tosylate with DXd ADCs for advanced solid tumors

A Phase 1b, Multicenter, Open-Label Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors

Phase 1 Interventional Daiichi Sankyo · NCT06244485

This study is testing a new treatment combining valemetostat tosylate with a specific type of cancer drug to see if it can help people with advanced solid tumors like certain types of gastric, lung, or breast cancer.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment210 (estimated)
Ages18 Years and up
SexAll
SponsorDaiichi Sankyo Industry-sponsored
Drugs / interventionstrastuzumab, chemotherapy, prednisone
Locations38 sites (Irvine, California and 37 other locations)
Trial IDNCT06244485 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd antibody-drug conjugates in patients with advanced solid tumors. It consists of two parts: a dose-escalation phase to determine the recommended dose for expansion, followed by a dose-expansion phase to further assess the safety and tolerability of the combination. The focus is on patients with HER2-positive gastric cancer, non-squamous non-small cell lung cancer, or unresectable or metastatic HER2 low breast cancer.

Who should consider this trial

Good fit: Ideal candidates are adults with unresectable or metastatic breast cancer, HER2-positive gastric cancer, or non-squamous NSCLC who have progressed on prior therapies.

Not a fit: Patients with solid tumors that are not HER2-positive or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are difficult to treat.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and antibody-drug conjugates, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria

All participants must meet all of the following criteria, as well as all criteria from the relevant sub-protocol to be eligible for enrollment:

* At least 18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
* Has at least 1 measurable lesion based on investigator imaging assessment (computed tomography or magnetic resonance imaging) using RECIST v 1.1 at Screening.
* Is willing to provide an adequate tumor sample.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.

Additional Key Inclusion for Sub-Protocol A:

* Diagnosed with pathologically documented breast cancer that:

  1. Is unresectable or metastatic.
  2. Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
  3. Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
  4. Has a history of low HER2 expression, defined as IHC 2+ /ISH-negative or IHC 1+ (ISH-negative or untested). ), as classified by the American Society of Clinical Oncology/College of American Pathologists 2018 HER2 testing guidelines.
  5. Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per American Society of Clinical Oncology/College of American Pathologists guidelines

     Additional Key Inclusion for Sub-Protocol B:

     • Gastric or GEJ adenocarcinoma that is (a) unresectable or metastatic or (b) has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen.

     Additional Key Inclusion for Sub-Protocol C:
* Pathologically documented Stage IIIB, IIIC, or IV non-squamous NSCLC with or without AGA at the time of enrollment.
* Must meet prior therapy requirements:

  * Participants without AGA: (a) received platinum-based chemotherapy in combination with α-PD-1/α -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy.
  * Participants with AGA: (a) has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for participant's genomic alteration at the time of Screening, (b) participants who have received platinum-based chemotherapy as a prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent

Key Exclusion Criteria

* Has previously been treated with any enhancer of zeste homolog inhibitors.
* Uncontrolled or significant cardiovascular disease.
* Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
* Has leptomeningeal carcinomatosis or metastasis.
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
* Current use of moderate or strong cytochrome P450 (CYP)3A inducers.
* Systemic treatment with corticosteroids (\>10 mg daily prednisone equivalents).
* History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
* Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous (IV) antibiotics, antivirals, or antifungals.
* Female who is pregnant or breastfeeding or intends to become pregnant during the study.
* Psychological, social, familial, or geographical factors that would prevent regular follow-up.

Additional Key Exclusion for Sub-Protocol A:

* Has previously received any anti-HER2 therapy in the metastatic setting.
* Has received prior treatment with an antibody-drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor, including either as part of prior treatment history or within prior participation in a clinical study.

Additional Key Exclusion for Sub-Protocol B:

\* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor.

Additional Key Exclusion for Sub-Protocol C:

\* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD

Where this trial is running

Irvine, California and 37 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Solid TumorValemetostat tosylateDXD Antibody-drug Conjugates
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.