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

Trial details

Who runs it

Daiichi Sankyo Inc.

Trial code

NCT06244485EU 2024-516916-93-00

Record updated

8 September 2026

Original description

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).Read full original descriptionShow less

A phase 1B, multicenter, open-label study of Valemetostat Tosylate in combination with DXd ADCs in subjects with solid tumors(study of Valemetostat Tosylate in combination with DXd ADCs)

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).

Inclusion: 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; 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; 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 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: 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.

ClinicalTrials.gov NCT06244485 · EU CTIS 2024-516916-93-00