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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT03734029
• Date of registration: 06/11/2018
• Prospective Registration: Yes
• Primary sponsor: Daiichi Sankyo
• Public title: Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
• Scientific title: A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
• Date of first enrolment: December 27, 2018
• Target sample size: 557
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03734029
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Canada, China, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Portugal, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Global Clinical Leader
• Affiliation: Daiichi Sankyo

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Nab-paclitaxel

Drug: Capecitabine

Drug: Eribulin

Drug: Trastuzumab deruxtecan (DS-8201a)

Drug: Gemcitabine

Drug: Paclitaxel

Primary Outcome(s)

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years]

Secondary Outcome(s)

Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) [Time Frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years]

Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [Time Frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years]

Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [Time Frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years]

Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients) [Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years]

Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years]

Overall Survival (OS) in All Patients [Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years]

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status [Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years]

Duration of Response in Participants With HER2-low Breast Cancer (All Patients) [Time Frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years]

Number of Overall Survival Events (Deaths) [Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years]

Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years]

Secondary ID(s)

184223

2018-003069-33

DESTINY-B04

DS8201-A-U303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Daiichi Sankyo Co., Ltd.

AstraZeneca

Results

• Results available: Yes
• Date Posted: 15/06/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03734029