Phase 1b Study of EZH1/2 Inhibitor Valemetostat in Combination With Trastuzumab Deruxtecan in Subjects With HER2 Low/Ultra-low/Null Metastatic Breast Cancer

NCT05633979 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0315NCI-2022-09968
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

To find a recommended dose of valemetostat that can be given in combination with trastuzumab deruxtecan to patients with low/ultra-low HER2-expressing metastatic breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• The Overall Response Rate (ORR)

  through study completion; an average of 2-3 years.

Study Arms (2)

Group 1

EXPERIMENTAL

Participants will receive the same drugs at the same schedule, and the same dose of trastuzumab deruxtecan

Drug: Trastuzumab deruxtecan; Drug: Valemetostat

Group 2

EXPERIMENTAL

Participants will only receive 1 dose level of valemetostat.

Drug: Valemetostat

Interventions

Trastuzumab deruxtecan DRUG

Given by IV (vein)

Group 1

Valemetostat DRUG

Given by PO

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the informed consent form (ICF) is signed.
• MBC or locally progressive breast cancer that is not a surgical candidate.
• Has progressed on and would no longer benefit from endocrine therapy in hormone receptor-positive subjects.
• Has been treated with at least 1 prior line of chemotherapy in the metastatic or locally progressive setting.
• Has adequate treatment washout period by the time of enrollment, defined as:
• Treatment Washout Period Major surgery ≥ 4 weeks Radiation therapy including palliative stereotactic radiation to chest ≥ 4 weeks Palliative stereotactic radiation therapy to other anatomic areas ≥ 2 weeks Anti-cancer chemotherapy (Immunotherapy \[non-antibody based therapy\]), retinoid therapy, hormonal therapy
• weeks Targeted agents and small molecules ≥ 2 weeks or 5 half-lives, whichever is longer Nitrosoureas or mitomycin C ≥ 6 weeks Antibody-based anti-cancer therapy ≥ 4 weeks Chloroquine/Hydroxychloroquine \>14 days
• Has at least one measurable lesion per RECIST (except for up to the first 5 subjects who enroll in dose escalation part where the measurable lesions meeting RECIST definition are not mandatory).
• Is willing to provide fresh tumor tissue via tumor biopsy only if the participant has a disease that can be safely accessed through a CT-guided/US-guided or percutaneous biopsy for multiple core biopsies judged by the investigator. If the participant doesn't have a disease that can be safely accessed, they are still eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Negative serum pregnancy test within 72 hours of receiving the first dose of the study medication for women of childbearing potential as per institutional guidelines. Post-menopausal women (defined as having no menses for at least 1 year) and surgically sterilized women are not required to undergo pregnancy tests.
• Subjects of childbearing potential must be willing to use effective birth control methods or be surgically sterile or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of the study drug (for males) and 7 months after last dose of study drug (for females). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for at least 1 year.
• Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 3 months after the final study drug administration.
• Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and for at least 3 months after the final study drug administration.
• The patient must have adequate organ function as determined by the following laboratory values:

You may not qualify if:

• Has previously been treated with any anti-HER2 therapy, including T-DXd, or EZH inhibitors.
• 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. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study registration.
• Prior malignancy active within the previous 2 years except for locally curable cancer that is currently considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer
• Uncontrolled or significant cardiovascular disease, including the following:
• LVEF \< 50% within 28 days
• Evidence of prolongation of QT/QTc (e.g., repeated episodes of QT corrected for heart rate using Fridericia's method \[QTcF\] \>450 ms) (average of triplicate determinations; over a 5 min time window when the subject has been supine position for at least 10 min without any environmental stimuli).
• Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome
• History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
• Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial fibrillation may be enrolled), or asymptomatic persistent ventricular tachycardia
• Subject has clinically relevant bradycardia of 50 bpm unless the subject has a pacemaker
• History of second or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers, within 6 months prior to Screening
• Myocardial infarction within 6 months prior to Screening
• Angioplasty or stent graft implantation within 6 months prior to Screening
• Uncontrolled angina pectoris within 6 months prior to Screening
• New York Heart Association (NYHA) Class 2-4 congestive heart failure

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Senthil Damodaran, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 1, 2022
• Study Start: February 9, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2032
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (1)