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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Sep 2025 → ongoing

Decision date (initial)

2025-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2024-516916-93-00

ClinicalTrials.gov

NCT06244485

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Safety

Master protocol Primary objective: Part 1 Dose-escalation Phase: To assess the safety and tolerability of valemetostat and each DXd ADC when administered in combination and determine the RDE. Part 2 Dose expansion Phase: To assess the efficacy of valemetostat and each DXd ADC when administered in combination. Part 2 Dose-expansion Phase: To assess the safety and tolerability of valemetostat and T-DXd when administered in combination(Sub-protocol A).

Secondary objectives 3

1. Part 1 Dose-escalation Phase and Part 2 Dose expansion Phase:To assess the efficacy of valemetostat and each DXd ADC when administered in combination
2. Part 2 Dose-expansion Phase: To assess the safety and tolerability of valemetostat and each DXd ADC when administered in combination (SubProtocols B and C)
3. To evaluate the PK of valemetostat and each DXd ADC when administered in combination

Conditions and MedDRA coding

This study will be a Phase 1b, global, multicenter, open-label, 2-part study of valemetostat in combination with DXd ADCs. The Master Protocol study design contains independent subprotocols, which have been defined by treatment combination and subject population, as follows: Sub-protocol A: Valemetostat in combination with T-DXd in subjects with previously treated, unresectable and/or metastatic HER2-low (immunohistochemistry[IHC] 1+ or IHC 2+/in situ hybridization [ISH]-negative) BC; for details, see Sub-protocol A. Sub-protocol B: Valemetostat in combination with T-DXd in subjects with previously treated, advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma; for details, see Sub-protocol B. Sub-protocol C: Valemetostat in combination with Dato-DXd in subjects with previously treated, locally advanced, unresectable, or metastatic non-squamous NSCLC with or without actionable genomic alteration(s); for details, see Sub-protocol C.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. All participants must meet all of the following criteria, as well as all criteria from the relevant sub-protocol to be eligible for enrolment: 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.
2. Additional Key Inclusion for Sub-Protocol A: 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
3. 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.
4. Additional Key Inclusion for Sub-Protocol C: Pathologically documented Stage IIIB, IIIC, or IV nonsquamous NSCLC with or without AGA at the time of enrolment. 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, and (b) participants who have received platinumbased 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 4

1. 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.
2. 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.
3. 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.
4. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation), Number of Participants Reporting Treatmentemergent Adverse Events (Part 1 Dose Escalation), Objective Response Rate Based on Investigator Assessment (Part 2 Dose Expansion)

Secondary endpoints 1

1. Overall survival, Progression-free Survival, Duration of Response (DoR), Objective Response Rate Based on Investigator Assessment (Part 1 Dose Escalation), Number of Participants Reporting Treatment-emergent Adverse Events (Part 2 Dose Expansion), Total and Unbound Plasma Concentration of Valemetostat, Plasma Concentration of DXd Antibody-Drug Conjugates

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 11

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications