Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer; HER2-positive; Metastatic

Treatments: Drug: Trastuzumab deruxtecan; Drug: Placebo; Drug: Taxane; Drug: Trastuzumab; Drug: Pertuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04784715

D967UC00001

2020-004074-21 (EudraCT Number)

2023-507904-30-00 (Registry Identifier)

Details and patient eligibility

About

The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.

Full description

Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab). 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.

Enrollment: 1,157 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must be ≥18 years of age

• Pathologically documented breast cancer that:

  1. is advanced or metastatic
  2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
  3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting

• No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to metastatic diagnosis.

• Has protocol-defined adequate organ and bone marrow function

• ECOG performance status 0 or 1

Key Exclusion Criteria:

• Ineligible for any of the agents on the study.
• Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
• Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
• Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
• Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,157 participants in 3 patient groups

Arm A

Experimental group

Description:

Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo

Treatment:

Drug: Placebo

Drug: Trastuzumab deruxtecan

Arm B

Experimental group

Description:

Trastuzumab deruxtecan (T-DXd) plus pertuzumab

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab deruxtecan

Arm C

Active Comparator group

Description:

Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Drug: Taxane