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

NCT06244485 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DS3201-324
• Study Type: interventional
• Target: 210
• Locations: 4 countries
• Sites: 38

Brief Summary

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

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; Valemetostat tosylate; DXD Antibody-drug Conjugates

Outcome Measures

Primary Outcomes (3)

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

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

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

  Screening up to 40 days after last dose

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

  Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 criteria. CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

  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)

• Overall Survival

  Date of enrollment up to date of death due to any cause, up to approximately 5 years

• Progression-free Survival

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

• Duration of Response (DoR)

  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

• Objective Response Rate Based on Investigator Assessment (Part 1 Dose Escalation)

  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

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

  Screening up to 40 days after last dose

Study Arms (6)

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

EXPERIMENTAL

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

Drug: Valemetostat tosylate; Drug: T-DXd

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

EXPERIMENTAL

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).

Drug: Valemetostat tosylate; Drug: Dato-DXd

Part 1: Dose Escalation (Sub-protocol A)

EXPERIMENTAL

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

Drug: Valemetostat tosylate; Drug: T-DXd

Part 2: Dose Expansion (Sub-protocol B)

EXPERIMENTAL

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.

Drug: Valemetostat tosylate; Drug: T-DXd

Part 2: Dose Expansion (Sub-protocol C)

EXPERIMENTAL

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).

Drug: Valemetostat tosylate; Drug: Dato-DXd

Part 2: Dose Expansion (Sub-protocol A)

EXPERIMENTAL

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.

Drug: Valemetostat tosylate; Drug: T-DXd

Interventions

Valemetostat tosylate DRUG

Administered orally once daily

Also known as: DS-3201b

Part 1: Dose Escalation (Sub-protocol A); Part 1: Dose Escalation Phase (Sub-protocol B); Part 1: Dose Escalation Phase (Sub-protocol C); Part 2: Dose Expansion (Sub-protocol A); Part 2: Dose Expansion (Sub-protocol B); Part 2: Dose Expansion (Sub-protocol C)

T-DXd DRUG

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

Also known as: DS-8201a, ENHERTU

Part 1: Dose Escalation (Sub-protocol A); Part 1: Dose Escalation Phase (Sub-protocol B); Part 2: Dose Expansion (Sub-protocol A); Part 2: Dose Expansion (Sub-protocol B)

Dato-DXd DRUG

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

Also known as: DS-1062a

Part 1: Dose Escalation Phase (Sub-protocol C); Part 2: Dose Expansion (Sub-protocol C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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.
• \* Participants who have received an antibody-drug conjugate consisting of an exatecan derivative that is a topoisomerase I inhibitor.
• \* Has received any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I or TROP2-targeted therapy including Dato-DXD

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (38)

City of Hope At Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

WITHDRAWN

Sharp Memorial Hospital

San Diego, California, 92123, United States

RECRUITING

Brcr Medical Center, Inc Dba Boca Raton Clinical Research

Plantation, Florida, 33322, United States

RECRUITING

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, 33612, United States

WITHDRAWN

University of Hawaii At Manoa

Honolulu, Hawaii, 96813, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

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

New York, New York, 10065, United States

RECRUITING

Clinical Research Alliance

Westbury, New York, 11590, United States

RECRUITING

Unc Hospitals

Chapel Hill, North Carolina, 27514, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

RECRUITING

Ut Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

WITHDRAWN

Next Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Peking University Third Hospital

Beijing, 100191, China

RECRUITING

Sun Yat-Sen University, Cancer Center

Guangzhou, 510060, China

RECRUITING

SunYat-Sen University Cancer Center

Guangzhou, 510060, China

RECRUITING

Harbin Medical Univeristy Cancer Hospital

Heilongjiang, 150081, China

RECRUITING

Hunan Cancer Hospital

Hunan, 410013, China

RECRUITING

Jilin Cancer Hospital

Jilin, 130000, China

RECRUITING

Jinana Center Hosptial

Shandong, 240013, China

RECRUITING

IRCCS Istituto Scientifico Romagnolo Per

Cesena, 47014, Italy

RECRUITING

National Cancer Center Hospital

Chūōku, 104-0045, Japan

RECRUITING

National Hospital Org-Kyushu Cancer Center

Fukuoka, 811-1395, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

RECRUITING

The Cancer Institute Hospital of Jfcr

Kōtoku, 135-8550, Japan

RECRUITING

Aichi Cancer Center Hospital

Nagoya, 464-8681, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, 540-0008, Japan

RECRUITING

Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

RECRUITING

Osaka University Hospital

Suita, 565-0871, Japan

RECRUITING

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

RECRUITING

MeSH Terms

Interventions

trastuzumab deruxtecan

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Central Study Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

9089926400; CTRinfo@dsi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: February 6, 2024
• Study Start: February 16, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (20); JP (10); IT (1); CN (7)