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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06244485
• Other study ID #: DS3201-324
• Status: Recruiting
• Phase: Phase 1
• Start date: February 16, 2024
• Est. completion date: November 1, 2028

Study information

• Verified date: June 2024
• Source: Daiichi Sankyo
• Contact: Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 9089926400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: November 1, 2028
• Est. primary completion date: November 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 A:

• Diagnosed with pathologically documented breast cancer that:

1. Is unresectable or metastatic.

2. Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects in the opinion of the investigator.

3. Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the recurrent or metastatic setting.

4. 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.

5. 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 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 a-PD-1/a -PD-L1 mAb as a prior line of therapy or (b) received platinum-based chemotherapy and a -PD-1/ a -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 a -PD-1/a -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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• Valemetostat tosylate
Administered orally once daily
• T-DXd
One IV infusion Q3W on Day 1 of each 21-day cycle
• Dato-DXd
One IV infusion Q3W on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku
Japan	National Cancer Center Hospital East	Kashiwa
Japan	The Cancer Institute Hospital of Jfcr	Koto-ku
Japan	Kindai University Hospital	Osaka-Sayama
Japan	Shizuoka Cancer Center	Sunto-gun
United States	Dana-Farber Cancer Institute - Parent.	Boston	Massachusetts
United States	Unc Hospitals	Chapel Hill	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mary Crowley Cancer Research Centers	Dallas	Texas
United States	Next Virginia	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Falls Church	Virginia
United States	University of Hawaii At Manoa	Honolulu	Hawaii
United States	University of Texas M. D. Anderson Cancer Center	Houston	Texas
United States	City of Hope At Orange County Lennar Foundation Cancer Center	Irvine	California
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan-Kettering Cancer Center (Mskcc) - New York	New York	New York
United States	Brcr Medical Center, Inc Dba Boca Raton Clinical Research	Plantation	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Sharp Memorial Hospital	San Diego	California
United States	Fred Hutch	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida
United States	Clinical Research Alliance	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation)		Cycle 1 Day 1 up to Day 21 (each cycle is 21 days)
Primary	Number of Participants Reporting Treatment-emergent Adverse Events (Part 1 Dose Escalation)		Screening up to 40 days after last dose
Primary	Objective Response Rate Based on Investigator Assessment (Part 2 Dose Expansion)	Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 criteria. CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years
Secondary	Overall Survival		Date of enrollment up to date of death due to any cause, up to approximately 5 years
Secondary	Progression-free Survival	Disease progression will be determined by investigator assessment of tumor scans and using RECIST v 1.1 criteria.	Date of enrollment up to date of radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 5 years
Secondary	Duration of Response (DoR)	CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	Date of first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause (whichever occurs first), up to approximately 5 years
Secondary	Objective Response Rate Based on Investigator Assessment (Part 1 Dose Escalation)	Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 criteria. CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.	Baseline (Screening), at every 6 weeks from Cycle 1 Day 1 in the first year, and every 12 weeks thereafter until disease progression or until the start of a new anticancer treatment, up to approximately 5 years
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events (Part 2 Dose Expansion)		Screening up to 40 days after last dose
Secondary	Total and Unbound Plasma Concentration of Valemetostat		Cycle 1, Day 1: Predose, 1 hour (hr), 2 hr, 4 hr, and 5 hr postdose; Cycle 1, Day 8 and Day 15: Predose; Cycles 2, 3, 4, Day 1: Predose (each cycle is 21 days)
Secondary	Plasma Concentration of DXd Antibody-Drug Conjugates		Cycle 1, Day 1: Predose, 1 hour (hr), 2 hr, 4 hr, and 5 hr postdose; Cycle 1, Day 8 and Day 15: Predose; Cycles 2, 3, 4, Day 1: Predose (each cycle is 21 days)