New drug cocktail aims to tackle Hard-to-Treat cancers

NCT ID NCT06244485

Disease control Sponsor: Daiichi Sankyo Source: ClinicalTrials.gov ↗

First seen Jun 24, 2026 · Last updated Sep 16, 2026 · Updated 5 times

Summary

This early-stage trial is testing whether combining valemetostat tosylate with two different antibody-drug conjugates (T-DXd or Dato-DXd) is safe and effective for people with advanced solid tumors. About 210 adults with at least one measurable tumor will receive the drugs orally and by IV. The study looks for side effects and tumor shrinkage.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: valemetostat tosylate combined with either T-DXd (Enhertu) or Dato-DXd
What this could lead to: If successful, this could point toward a new combination treatment for advanced solid tumors that are hard to treat.
What could go wrong: This is an early Phase 1b trial, so safety and effectiveness are not yet proven. The combination may cause unexpected side effects or fail to shrink tumors.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

About 210 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2024

Expected to finish

Nov 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 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: * 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 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. 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 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 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

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Conditions

The condition(s) this trial relates to.

breast cancer gastric adenocarcinoma gastroesophageal junction adenocarcinoma non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced solid tumor

Contacts and locations

Locations

Aichi Cancer Center Hospital

Nagoya, 464-8681, Japan
Brcr Medical Center, Inc Dba Boca Raton Clinical Research

Plantation, Florida, 33322, United States
City of Hope At Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States
Clinical Research Alliance

Westbury, New York, 11590, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States
Harbin Medical Univeristy Cancer Hospital

Heilongjiang, 150081, China
Hunan Cancer Hospital

Hunan, 410013, China
IRCCS Istituto Scientifico Romagnolo Per

Cesena, 47014, Italy
Jilin Cancer Hospital

Jilin City, 130000, China
Jinana Center Hosptial

Shandong, 240013, China
Kanagawa Cancer Center

Yokohama, 241-8515, Japan
Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan
Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States
Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Memorial Sloan-Kettering Cancer Center (Mskcc) - New York

New York, New York, 10065, United States
National Cancer Center Hospital

Chūōku, 104-0045, Japan
National Cancer Center Hospital East

Kashiwa, 277-8577, Japan
National Hospital Org-Kyushu Cancer Center

Fukuoka, 811-1395, Japan
Next Virginia

Fairfax, Virginia, 22031, United States
Osaka International Cancer Institute

Osaka, 540-0008, Japan
Osaka University Hospital

Suita, 565-0871, Japan
Peking University Third Hospital

Beijing, 100191, China
Providence Portland Medical Center

Portland, Oregon, 97213, United States
Sharp Memorial Hospital

San Diego, California, 92123, United States
Shizuoka Cancer Center

Shizuoka, 411-8777, Japan
Sun Yat-Sen University, Cancer Center

Guangzhou, 510060, China
SunYat-Sen University Cancer Center

Guangzhou, 510060, China
The Cancer Institute Hospital of Jfcr

Kōtoku, 135-8550, Japan
The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States
Unc Hospitals

Chapel Hill, North Carolina, 27514, United States
University of Chicago Medical Center

Chicago, Illinois, 60637, United States
University of Hawaii At Manoa

Honolulu, Hawaii, 96813, United States
University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States
Ut Southwestern Medical Center

Dallas, Texas, 75390, United States

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