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Advanced Solid TumorPhase 1NCT06244485

A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors

A Phase 1 study testing Valemetostat tosylate, T-DXd and Dato-DXd in people with Advanced Solid Tumor, run by Daiichi Sankyo at 35 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd antibody-drug conjugates (ADC) in participants with advanced solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor
What is being tested?
Valemetostat tosylate, T-DXd and Dato-DXd
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
35 sitesin 4 countries
Study dates
22 Feb 2024to 1 Nov 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 informed consent form (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:
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  • Diagnosed with pathologically documented breast cancer that:
  • Is unresectable or metastatic.
  • Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.
  • Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.
  • Has a history of low HER2 expression, defined as immunohistochemistry (IHC) 2+ /in situ hybridization (ISH)-negative or IHC 1+ (ISH-negative or untested), as classified by the American Society of Clinical Oncology/College of American Pathologists 2023 HER2 testing guidelines.
  • 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 gastro-esophageal junction (GEJ) adenocarcinoma that is (a) unresectable or metastatic (b) has progressed on HER2-directed monoclonal antibody (mAb) containing therapy, such as 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 actionable genomic alterations (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 the only prior line of therapy or (b) received platinum-based chemotherapy and α -PD-1/ α -PD-L1 mAb (in either order) sequentially as the only 2 prior lines of therapy.
  • Participants with AGA: (a) has been treated with 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 the only prior line of cytotoxic therapy, (c) may have received α -PD-1/α -PD-L1 mAb alone or in combination with a cytotoxic agent

Who cannot join

  • 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.
Show all 18Show fewer
  • 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

Trial locations and contacts

35 sites in 4 countries.

35 sites in 4 countries

United States17 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Unc Hospitals

    Chapel Hill, North Carolina, 27514

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Mary Crowley Cancer Research Centers

    Dallas, Texas, 75230

  • Ut Southwestern Medical Center

    Dallas, Texas, 75390

  • Next Virginia

    Fairfax, Virginia, 22031

  • University of Hawaii At Manoa

    Honolulu, Hawaii, 96813

  • University of Texas M. D. Anderson Cancer Center

    Houston, Texas, 77030

  • City of Hope At Orange County Lennar Foundation Cancer Center

    Irvine, California, 92618

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Memorial Sloan-Kettering Cancer Center (Mskcc) - New York

    New York, New York, 10065

  • Brcr Medical Center, Inc Dba Boca Raton Clinical Research

    Plantation, Florida, 33322

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Sharp Memorial Hospital

    San Diego, California, 92123

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Clinical Research Alliance

    Westbury, New York, 11590

Other trials in United States

Japan10 sites

  • National Cancer Center Hospital

    Chūōku, 104-0045

  • National Hospital Org-Kyushu Cancer Center

    Fukuoka, 811-1395

  • National Cancer Center Hospital East

    Kashiwa, 277-8577

  • The Cancer Institute Hospital of Jfcr

    Kōtoku, 135-8550

  • Aichi Cancer Center Hospital

    Nagoya, 464-8681

  • Osaka International Cancer Institute

    Osaka, 540-0008

  • Kindai University Hospital

    Ōsaka-sayama, 589-8511

  • Shizuoka Cancer Center

    Shizuoka, 411-8777

  • Osaka University Hospital

    Suita, 565-0871

  • Kanagawa Cancer Center

    Yokohama, 241-8515

Other trials in Japan

China7 sites

  • Peking University Third Hospital

    Beijing, 100191

  • Sun Yat-Sen University, Cancer Center

    Guangzhou, 510060

  • SunYat-Sen University Cancer Center

    Guangzhou, 510060

  • Harbin Medical Univeristy Cancer Hospital

    Heilongjiang, 150081

  • Hunan Cancer Hospital

    Hunan, 410013

  • Jilin Cancer Hospital

    Jilin City, 130000

  • Jinana Center Hosptial

    Shandong, 240013

Other trials in China

Italy1 site

  • IRCCS Istituto Scientifico Romagnolo Per

    Cesena, 47014

Other trials in Italy

About this study

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

This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd antibody-drug conjugates (ADC) in participants with advanced solid tumors.

Read the detailed description

This is a 2-part study of valemetostat in combination with DXd ADCs in participants with human epidermal growth factor 2 (HER2)-positive gastric cancer, non-squamous non-small cell lung cancer (NSCLC), or unresectable or metastatic HER2 low breast cancer. The study will begin with a Part 1 Dose-escalation Phase and will continue until the recommended dose for expansion "RDE" of valemetostat is determined and will then be followed by a Part 2 Dose-expansion Phase to further evaluate the safety and tolerability of the combination.

Being tested
Valemetostat tosylate, T-DXd, Dato-DXd
Keywords
Advanced Solid Tumor, Valemetostat tosylate, DXD Antibody-drug Conjugates

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Valemetostat tosylateDrug

    Also called DS-3201b

    Administered orally once daily

  • T-DXdDrug

    Also called DS-8201a, ENHERTU

    One IV infusion Q3W on Day 1 of each 21-day cycle

  • Dato-DXdDrug

    Also called DS-1062a

    One IV infusion Q3W on Day 1 of each 21-day cycle.

Study groups in NCT06244485
Study groupRoleWhat they receive
Part 1: Dose Escalation Phase (Sub-protocol B)ExperimentalParticipants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat in combination with T-DXd.
Receives: Drug: Valemetostat tosylate; Drug: T-DXd
Part 1: Dose Escalation Phase (Sub-protocol C)ExperimentalParticipants with previously treated, locally advanced, unresectable, or metastatic non-squamous NSCLC with or without actionable genomic alteration(s) will receive valemetostat in combination with datopotamab deruxtecan (Dato-DXd).
Receives: Drug: Valemetostat tosylate; Drug: Dato-DXd
Part 1: Dose Escalation (Sub-protocol A)ExperimentalParticipants with unresectable or metastatic HER2-low IHC]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat in combination with T-DXd.
Receives: Drug: Valemetostat tosylate; Drug: T-DXd
Part 2: Dose Expansion (Sub-protocol B)ExperimentalParticipants with previously treated, advanced, or metastatic HER2-positive gastric or GEJ adenocarcinoma will receive valemetostat at the RDE in combination with T-DXd at RDE.
Receives: Drug: Valemetostat tosylate; Drug: T-DXd
Part 2: Dose Expansion (Sub-protocol C)ExperimentalParticipants with previously treated, locally advanced, unresectable, or metastatic non-squamous NSCLC with or without actionable genomic alteration(s) will receive valemetostat at the RDE in combination with Dato-DXd.
Receives: Drug: Valemetostat tosylate; Drug: Dato-DXd
Part 2: Dose Expansion (Sub-protocol A)ExperimentalParticipants with unresectable or metastatic HER2-low IHC]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat at the RDE in combination with T-DXd at RDE.
Receives: Drug: Valemetostat tosylate; Drug: T-DXd

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation)

    Measured: Cycle 1 Day 1 up to Day 21 (each cycle is 21 days)

  2. Number of Participants Reporting Treatment-emergent Adverse Events (Part 1 Dose Escalation)

    Measured: Screening up to 40 days after last dose, up to approximately 5 years

  3. Objective Response Rate Based on Investigator Assessment (Part 2 Dose Expansion)

    Measured: Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years

Secondary outcomes (7)

  1. Overall Survival

    Measured: Date of first dose up to date of death due to any cause, up to approximately 5 years

  2. Progression-free Survival

    Progression-free survival will be assessed by RECIST v 1.1 criteria.

    Measured: Date of first dose up to date of radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 5 years

  3. Duration of Response (DoR)

    Measured: Date of first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause (whichever occurs first), up to approximately 5 years

  4. Objective Response Rate Per Investigator Assessment Based on RECIST v1.1 (Part 1 Dose Escalation)

    Measured: Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years

  5. Number of Participants Reporting Treatment-emergent Adverse Events (Part 2 Dose Expansion)

    Measured: Screening up to 40 days after last dose, up to approximately 5 years

  6. Total and Unbound Plasma Concentration of Valemetostat

    Measured: Cycle 1, Day 1 up to approximately 5 years (cycle length=21 days)

  7. Plasma Concentration of DXd Antibody-Drug Conjugates

    Measured: Cycle 1, Day 1 up to approximately 5 years (cycle length=21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2024
  2. Study start22 Feb 2024
  3. Primary completion1 Nov 2028 (estimated)
  4. Study completion1 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
210 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06244485
Sponsor's protocol ID
DS3201-324
Other IDs
2024-516916-93-00, jRCT2031230614
Status last verified
Sep 2026
First submitted
29 Jan 2024
Last updated
15 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Valemetostat tosylate, T-DXd and Dato-DXd in people with Advanced Solid Tumor, run by Daiichi Sankyo at 35 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Japan, China, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation) (time frame: Cycle 1 Day 1 up to Day 21 (each cycle is 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06244485.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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