A Phase 1b, Multicenter, Open-Label Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors

DS3201-324

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

2024-02-16

2028-11-01

2028-11-01

Recruiting

Early phase I

140

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 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 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 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 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 140, 'type': 'ESTIMATED'}}

2024-04-15