Study of Valemetostat in Combination with DXd ADCs

JRCT ID: jRCT2031230614

Registered date:01/02/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid Tumors
• Date of first enrollment: 29/02/2024
• Target sample size: 140
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Valemetostat tosylate (DS-3201b) will be administered once daily.
T-DXd (DS-8201a, ENHERTU) will be administered every 21 days.
Dato-DXd (DS-1062a) will be administered every 21days.

Outcome(s)

Primary Outcome

Part 1: Incidence of dose-limiting toxicities (DLTs), incidence of treatment-emergent adverse events (TEAEs)
Part 2: objective response rate (ORR)

Secondary Outcome

overall survival (OS), progression-free survival (PFS), duration of response (DoR), pharmacokinetic (PK)
Part 1: ORR
Part 2: Incidence of TEAEs

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Master Protocol Key Inclusion Criteria

- 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 Criteria for Sub-protocol B
- Diagnosed with pathologically documented gastric or GEJ adenocarcinoma that:
- Is unresectable or metastatic.
- Has progressed on trastuzumab or approved trastuzumab biosimilar-containing regimen.

Additional Key Inclusion Criteria for Sub-protocol C
- Has pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous NSCLC with or without AGAs at the time of enrollment.
- Subject must meet the following prior therapy requirements:
- Subjects without AGA:
- Received platinum-based chemotherapy in combination with a-programmed cell death protein (PD-1)/a-programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) as a prior line of therapy.
OR
- Received platinum-based chemotherapy and a-PD-1/a-PD-L1 mAb (in either order) sequentially as 2 prior lines of therapy.
- Subjects with AGA:
- Has been treated with at least 1 or 2 prior lines of applicable targeted therapy that is locally approved for the subject's genomic alteration at the time of Screening.
- Subjects who have received platinum-based chemotherapy as a prior line of cytotoxic therapy.
- May have received a-PD-1/a-PD-L1 mAb alone or in combination with a cytotoxic agent.

Exclude criteria

Master Protocol Key Exclusion Criteria
- Has previously been treated with any EZH 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. (>10mg 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 Criteria for Sub-protocol B
- Subjects who have received an ADC consisting of an exatecan derivative that is a topoisomerase I inhibitor.

Additional Key Exclusion Criteria 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.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary ID(s): NCT06244485