Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: HER2-positive Early Breast Cancer; Breast Cancer; Breast Neoplasms

Treatments: Drug: Pertuzumab; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Trastuzumab; Drug: Trastuzumab Deruxtecan; Drug: cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05113251

D967RC00001

2021-000603-21 (EudraCT Number)

Details and patient eligibility

About

This study will look at the efficacy and safety of trastuzumab deruxtecan (T-DXd) in a neoadjuvant setting, in high-risk, HER2-positive early non-metastatic breast cancer.

Full description

The target population of interest in this study is participants with high-risk HER2-positive early-stage breast cancer. The purpose of this study is to determine the efficacy and safety of T-DXd neoadjuvant therapy.

Participants will be randomised to one of 3 arms: T-DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).

Enrollment: 927 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must be at least 18 years of age.
• Histologically documented HER2-positive early breast cancer (EBC) participants, including clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition
• ECOG performance status of 0 or 1 at randomization
• Adequate organ and bone marrow function
• LVEF ≥ 50% within 28 days before randomization
• FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician

Exclusion Criteria:

• prior history of invasive breast cancer
• stage IV breast cancer (determined by AJCC staging system)
• any primary malignancy within 3 years (except resected non-melanoma skin cancer, curatively treated in situ disease) Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer)
• history of DCIS (except those treated with mastectomy >5 years prior to current diagnosis)
• History of, or current, ILD/pneumonitis
• Prior systemic therapy for the treatment of breast cancer
• Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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927 participants in 3 patient groups

Arm A

Experimental group

Description:

Trastuzumab deruxtecan

Treatment:

Drug: Trastuzumab Deruxtecan

Arm B

Experimental group

Description:

T-DXd, followed by THP

Treatment:

Drug: Trastuzumab Deruxtecan

Drug: Trastuzumab

Drug: Paclitaxel

Drug: Pertuzumab

Arm C

Active Comparator group

Description:

doxorubicin and cyclophosphamide, followed by THP

Treatment:

Drug: cyclophosphamide

Drug: Doxorubicin

Drug: Trastuzumab

Drug: Paclitaxel

Drug: Pertuzumab