A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
- Registration Number
- 2024-516916-93-00
- Lead Sponsor
- Daiichi Sankyo Inc.
- Brief Summary
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).
- Detailed Description
This is a 2-part study of valemetostat in combination with DXd ADCs in patients with HER2-positive gastric cancer, non-squamous NSCLC, or unresectable or metastatic HER2 low breast cancer. The study will begin with a Part 1 Dose-escalation Phase and will continue until the recommended dose for expansion "RDE" of valemetostat is determined and will then be followed by a Part 2 Dose-expansion Phase to further evaluate the safety and tolerability of the combination.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Not specified
- Target Recruitment
- 45
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
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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Primary Outcome Measures
Name Time Method 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) 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 Outcome Measures
Name Time Method 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 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
Trial Locations
- Locations (35)
City of Hope At Orange County Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Brcr Medical Center, Inc Dba Boca Raton Clinical Research
🇺🇸Plantation, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸Tampa, Florida, United States
University of Hawaii At Manoa
🇺🇸Honolulu, Hawaii, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center (Mskcc) - New York
🇺🇸New York, New York, United States
Clinical Research Alliance
🇺🇸Westbury, New York, United States
Scroll for more (25 remaining)City of Hope At Orange County Lennar Foundation Cancer Center🇺🇸Irvine, California, United States