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

NCT ID: NCT06244485

Last Updated: 2026-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-16

Study Completion Date

2028-11-01

Brief Summary

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This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.

Detailed Description

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This is a 2-part study of valemetostat in combination with DXd ADCs in patients with HER2-positive gastric cancer, non-squamous 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.

Conditions

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Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: Dose Escalation Phase (Sub-protocol B)

Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat in combination with T-DXd.

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

T-DXd

Intervention Type DRUG

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

Part 1: Dose Escalation Phase (Sub-protocol C)

Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat in combination with datopotamab deruxtecan (Dato-DXd).

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

Dato-DXd

Intervention Type DRUG

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

Part 1: Dose Escalation (Sub-protocol A)

Participants with unresectable or metastatic HER2-low IHC\]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat in combination with T-DXd.

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

T-DXd

Intervention Type DRUG

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

Part 2: Dose Expansion (Sub-protocol B)

Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat at the RDE in combination with T-DXd at RDE.

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

T-DXd

Intervention Type DRUG

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

Part 2: Dose Expansion (Sub-protocol C)

Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat at the RDE in combination with datopotamab deruxtecan (Dato-DXd).

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

Dato-DXd

Intervention Type DRUG

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

Part 2: Dose Expansion (Sub-protocol A)

Participants 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.

Group Type EXPERIMENTAL

Valemetostat tosylate

Intervention Type DRUG

Administered orally once daily

T-DXd

Intervention Type DRUG

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

Interventions

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Valemetostat tosylate

Administered orally once daily

Intervention Type DRUG

T-DXd

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

Intervention Type DRUG

Dato-DXd

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

Intervention Type DRUG

Other Intervention Names

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DS-3201b DS-8201a ENHERTU DS-1062a

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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City of Hope At Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Site Status RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status WITHDRAWN

Sharp Memorial Hospital

San Diego, California, United States

Site Status RECRUITING

Brcr Medical Center, Inc Dba Boca Raton Clinical Research

Plantation, Florida, United States

Site Status RECRUITING

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

Site Status WITHDRAWN

University of Hawaii At Manoa

Honolulu, Hawaii, United States

Site Status RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

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

New York, New York, United States

Site Status RECRUITING

Clinical Research Alliance

Westbury, New York, United States

Site Status RECRUITING

Unc Hospitals

Chapel Hill, North Carolina, United States

Site Status RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Providence Portland Medical Center

Portland, Oregon, United States

Site Status RECRUITING

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Site Status RECRUITING

Ut Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status WITHDRAWN

Next Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Peking University Third Hospital

Beijing, , China

Site Status RECRUITING

Sun Yat-Sen University, Cancer Center

Guangzhou, , China

Site Status RECRUITING

SunYat-Sen University Cancer Center

Guangzhou, , China

Site Status RECRUITING

Harbin Medical Univeristy Cancer Hospital

Heilongjiang, , China

Site Status RECRUITING

Hunan Cancer Hospital

Hunan, , China

Site Status RECRUITING

Jilin Cancer Hospital

Jilin, , China

Site Status RECRUITING

Jinana Center Hosptial

Shandong, , China

Site Status RECRUITING

IRCCS Istituto Scientifico Romagnolo Per

Cesena, , Italy

Site Status RECRUITING

National Cancer Center Hospital

Chūōku, , Japan

Site Status RECRUITING

National Hospital Org-Kyushu Cancer Center

Fukuoka, , Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa, , Japan

Site Status RECRUITING

The Cancer Institute Hospital of Jfcr

Kōtoku, , Japan

Site Status RECRUITING

Aichi Cancer Center Hospital

Nagoya, , Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, , Japan

Site Status RECRUITING

Kindai University Hospital

Ōsaka-sayama, , Japan

Site Status RECRUITING

Shizuoka Cancer Center

Shizuoka, , Japan

Site Status RECRUITING

Osaka University Hospital

Suita, , Japan

Site Status RECRUITING

Kanagawa Cancer Center

Yokohama, , Japan

Site Status RECRUITING

Countries

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United States China Italy Japan

Central Contacts

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Daiichi Sankyo Contact for Clinical Trial Information

Role: CONTACT

9089926400

Other Identifiers

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DS3201-324

Identifier Type: -

Identifier Source: org_study_id

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