A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors
- Conditions
- Advanced Solid Tumor
- Interventions
- Registration Number
- NCT06244485
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
This study will evaluate the safety, tolerability, and efficacy of valemetostat tosylate in combination with DXd ADC in patients with advanced solid tumors.
- 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
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Dose Escalation Phase (Sub-protocol C) Valemetostat tosylate Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat in combination with datopotamab deruxtecan (Dato-DXd). Part 1: Dose Escalation Phase (Sub-protocol B) Valemetostat tosylate Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat in combination with T-DXd. Part 1: Dose Escalation Phase (Sub-protocol B) T-DXd Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat in combination with T-DXd. Part 1: Dose Escalation (Sub-protocol A) Valemetostat tosylate Participants with unresectable or metastatic HER2-low IHC\]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat in combination with T-DXd. Part 2: Dose Expansion (Sub-protocol B) Valemetostat tosylate Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat at the RDE in combination with T-DXd at RDE. Part 2: Dose Expansion (Sub-protocol B) T-DXd Participants with previously treated, advanced, or metastatic HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma will receive valemetostat at the RDE in combination with T-DXd at RDE. Part 2: Dose Expansion (Sub-protocol C) Valemetostat tosylate Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat at the RDE in combination with datopotamab deruxtecan (Dato-DXd). Part 2: Dose Expansion (Sub-protocol A) Valemetostat tosylate Participants with unresectable or metastatic HER2-low IHC\]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat at the RDE in combination with T-DXd at RDE. Part 2: Dose Expansion (Sub-protocol A) T-DXd Participants with unresectable or metastatic HER2-low IHC\]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat at the RDE in combination with T-DXd at RDE. Part 1: Dose Escalation (Sub-protocol A) T-DXd Participants with unresectable or metastatic HER2-low IHC\]1+ or IHC 2+/ISH-negative breast cancer will receive valemetostat in combination with T-DXd. Part 1: Dose Escalation Phase (Sub-protocol C) Dato-DXd Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat in combination with datopotamab deruxtecan (Dato-DXd). Part 2: Dose Expansion (Sub-protocol C) Dato-DXd Participants with previously treated, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer (NSCLC) with or without actionable genomic alteration(s) will receive valemetostat at the RDE in combination with datopotamab deruxtecan (Dato-DXd).
- Primary Outcome Measures
Name Time Method Objective Response Rate Based on Investigator Assessment (Part 2 Dose Expansion) 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 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.
Number of Participants Reporting Dose-limiting Toxicities (Part 1 Dose Escalation) Cycle 1 Day 1 up to Day 21 (each cycle is 21 days) Number of Participants Reporting Treatment-emergent Adverse Events (Part 1 Dose Escalation) Screening up to 40 days after last dose
- Secondary Outcome Measures
Name Time Method Overall Survival Date of enrollment up to date of death due to any cause, up to approximately 5 years Progression-free Survival Date of enrollment up to date of radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 5 years Disease progression will be determined by investigator assessment of tumor scans and using RECIST v 1.1 criteria.
Duration of Response (DoR) 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 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.
Objective Response Rate Based on Investigator Assessment (Part 1 Dose Escalation) 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 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.
Number of Participants Reporting Treatment-emergent Adverse Events (Part 2 Dose Expansion) Screening up to 40 days after last dose 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) 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)
Trial Locations
- Locations (31)
City of Hope At Orange County Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
Memorial Sloan-Kettering Cancer Center (Mskcc) - New York
🇺🇸New York, New York, United States
Clinical Research Alliance
🇺🇸Westbury, New York, United States
Unc Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute - Parent.
🇺🇸Boston, Massachusetts, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
University of Hawaii At Manoa
🇺🇸Honolulu, Hawaii, 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
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Mary Crowley Cancer Research Centers
🇺🇸Dallas, Texas, United States
University of Texas M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Next Virginia
🇺🇸Fairfax, Virginia, United States
Fred Hutch
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
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
🇯🇵Shizuoka, Japan
Ut Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Sun Yat-Sen University, Cancer Center
🇨🇳Guangzhou, China
National Hospital Org-Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵Suita, Japan