A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer (DB-07)
Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, HER2-positive, Brain Metastases, Trastuzumab Deruxtecan, T-DXd, DS-8201a, DESTINY-Breast07, Anti-HER2 Antibody Drug Conjugate (ADC)
Eligibility Criteria
Key Inclusion Criteria:
- Patients must be at least 18 years of age
Pathologically documented breast cancer that:
- Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
- HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
- Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
- Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
- ECOG Performance Status of 0 or 1
Part 1
- Disease progression on or after the last systemic therapy prior to starting study treatment
- At least 1 prior treatment line in metastatic setting required.
Part 2 (Modules 0 - 5)
a) No prior lines of therapy for advanced/MBC allowed
- Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed
CNS Inclusion
- Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
- Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy
Key Exclusion Criteria:
- Uncontrolled or significant cardiovascular disease
- Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Spinal cord compression or a history of leptomeningeal carcinomatosis
- Prior treatment with immune checkpoint inhibitors
- Prior treatment with an ADC containing a topoisomerase I inhibitor
- Prior treatment with tucatinib
CNS Exclusion
- Modules 0 - 5: Has untreated brain metastasis
- Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Module 1- T-DXd and Durvalumab
Module 2- T-DXd and Pertuzumab
Module 3- T-DXd and Paclitaxel
Module 4- T-DXd and Durvalumab and Paclitaxel
Module 0- T-DXd
Module 5 - T-DXd and Tucatanib
Module 6 - T-DXd and Tucatinib
Module 7 - T-DXd
T-DXd and Durvalumab
T-DXd and Pertuzumab
T-DXd and Paclitaxel
T-DXd and Durvalumab and Paclitaxel
T-DXd
T-DXd and tucatinib
T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)
T-DXd monotherapy in patients with active brain metastases (Part 2 Only)