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

Study of Valemetostat in Combination with DXd ADCs

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Recruiting

Feb. 29, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

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 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 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.

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 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 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.

Both

Solid Tumors

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.

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

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

+81-3-3520-0111

Jan. 09, 2024

Yes

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Information: -Study Protocol -Statistical Analysis Plan (SAP) -Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

United States