A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer (DB-08)
Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, HER2-negative, HER2-low, Trastuzumab Deruxtecan, T-DXd, DS-8201a, DESTINY-Breast08, Anti-HER2 Antibody Drug Conjugate (ADC), Triple-negative breast cancer (TNBC)
Eligibility Criteria
Key Inclusion Criteria:
- Patients must be at least 18 years of age
Male or female patients who have pathologically documented breast cancer that:
- Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
- 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.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Module 1: T-DXd + capecitabine
Module 2: T-DXd + durvalumab + paclitaxel
Module 3: T-DXd + capivasertib
Module 4: T-DXd + anastrozole
Module 5: T-DXd + fulvestrant
T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use
T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use
T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use
T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral
T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use