Vanderbilt Clinical Trials

Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

Purpose

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Condition

Advanced or Metastatic Breast Cancer

Eligibility

Eligible Ages: Between 18 Years and 105 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Patients must be ≥18 years of age - Pathologically documented breast cancer that: 1. is advanced or metastatic 2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested) 3. has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting 4. was never previously HER2-positive 5. is documented HR+ disease in the metastatic setting. - No prior chemotherapy for advanced or metastatic breast cancer. - Has adequate tumor samples for assessment of HER2 status - Must have either: 1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or 2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting. - Has protocol-defined adequate organ and bone marrow function

Exclusion Criteria

Ineligible for all options in the investigator's choice chemotherapy arm - Lung-specific intercurrent clinically significant illnesses - Uncontrolled or significant cardiovascular disease or infection - Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening. - Patients with spinal cord compression or clinically active central nervous system metastases - Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment - Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).
Primary Purpose: Treatment
Masking: None (Open Label)
Masking Description: This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.

Arm Groups

Arm	Description	Assigned Intervention
Experimental Trastuzumab deruxtecan	Trastuzumab deruxtecan (T-DXd; DS-8201a) arm	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other names: DS-8201a; T-DXd
Active Comparator Standard of Care	Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm	Drug: Capecitabine Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally. Drug: Paclitaxel Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion. Drug: Nab-Paclitaxel Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

More Details

Status: Active, not recruiting
Sponsor: AstraZeneca

Study Contact

Detailed Description

Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer. The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.