Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

Daiichi Sankyo

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Eribulin; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Gemcitabine; Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03734029

DS8201-A-U303

184223 (Registry Identifier)

2018-003069-33 (EudraCT Number)

DESTINY-B04 (Other Identifier)

Details and patient eligibility

About

This study will compare DS-8201a to physician choice standard treatment.

Participants must have HER2-low breast cancer that has been treated before.

Participants' cancer:

• Cannot be removed by an operation
• Has spread to other parts of the body

Full description

This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.

Enrollment: 557 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is the age of majority in their country

• Has pathologically documented breast cancer that:

  1. Is unresectable or metastatic
  2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
  3. Is HR-positive or HR-negative
  4. Has progressed on, and would no longer benefit from, endocrine therapy
  5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
  6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)

• Has documented radiologic progression (during or after most recent treatment)

• Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:

  1. assessment of HER2 status
  2. assessment of post-treatment status

• Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1

• Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions

• Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)

Exclusion criteria

• Is ineligible for all options in the physician's choice arm
• Has breast cancer ever assessed with high-HER2 expression
• Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
• Has uncontrolled or significant cardiovascular disease
• Has spinal cord compression or clinically active central nervous system metastases
• Has history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
• Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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557 participants in 2 patient groups

Trastuzumab deruxtecan

Experimental group

Description:

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a

Treatment:

Drug: Trastuzumab deruxtecan (DS-8201a)

Physician's Choice

Active Comparator group

Description:

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options: * Capecitabine * Eribulin * Gemcitabine * Paclitaxel * Nab-paclitaxel

Treatment:

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Capecitabine

Drug: Eribulin

Drug: Gemcitabine