NCT05633979

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Primary Objectives: Dose escalation part: 1. To evaluate the safety and determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of valemetostat in combination with trastuzumab deruxtecan (T-DXd). Dose expansion part: 2. To evaluate the objective response rate (ORR) of valemetostat at the RDE in combination with T-DXd. Secondary Objectives: Dose escalation: 1. To determine ORR; defined as a percentage of subjects who achieve complete response (CR) or partial response (PR) by RECIST 1.1 criteria. 2. To determine survival outcomes, including duration of response (DoR), progression free survival (PFS), and overall survival (OS). 3. To determine the Clinical Benefit Rate (CBR) defined as stable disease (SD) ≥ 16 weeks + PR + CR. Dose expansion: 1. To determine survival outcomes, including DoR, PFS, and OS. * DOR of the proposed treatment: the time from observing response to the valemetostat treatment until objective tumor progression (PD) * PFS: the time from starting valemetostat treatment until objective tumor progression (PD) or death due to any cause. * Overall survival (OS): the time from starting valemetostat treatment until death due to any cause. 2. To determine the CBR defined as SD ≥16 weeks + PR + CR. 3. To evaluate safety of valemetostat in combination with T-DXd. 4. To evaluate the pharmacokinetics (PK) of both the drugs in combination. 5. To evaluate the immunogenicity of T-DXd Exploratory Objectives: 1. To investigate pharmacodynamic biomarkers. 2. To investigate biomarkers that may aid in identifying subjects who may derive clinical benefit.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab deruxtecan	Given by IV (vein)
DRUG	Valemetostat	Given by PO

Timeline

• Start date: 2023-02-09
• Primary completion: 2030-12-31
• Completion: 2032-12-31
• First posted: 2022-12-01
• Last updated: 2026-01-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study