A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

• Status: Recruiting
• Trial end date: 2023-08-28
• Target enrollment: 0
• Participant gender: All

Summary

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Daiichi Sankyo Company, Limited
• Treatments: Anastrozole; Capecitabine; Durvalumab; Fulvestrant; Paclitaxel; Trastuzumab

Criteria

Key Inclusion Criteria:

• Patients must be at least 18 years of age

• Male or female patients who have pathologically documented breast cancer that:

1. Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay

2. Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting

• Patient must have adequate tumor sample for biomarker assessment

• ECOG Performance Status of 0 or 1

For patients with HR+ disease:

Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required.

Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.

For patients with HR- disease:

Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5.

Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.

Key Exclusion Criteria:

• Uncontrolled intercurrent illness

• Uncontrolled or siginificant cardiovascular disease

• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

• Lung-specific intercurrent clinically significant illnesses

• Has spinal cord compression or clinically active central nervous system metastases

• Active primary immunodeficiency

• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

• Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.