A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer - DB-07

Study identifier:D967JC00001

ClinicalTrials.gov identifier:NCT04538742

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination with other Anti-cancer Agents in Patients with HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)

Medical condition

Metastatic Breast Cancer

Phase

Phase 1/2

Healthy volunteers

Study drug

Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Trastuzumab deruxtecan, Durvalumab, Durvalumab, Paclitaxel, Paclitaxel, Pertuzumab, Tucatinib, Tucatinib

Sex

All

Actual enrollment

450

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 28 Dec 2020

Estimated Primary Completion Date: 30 Dec 2024

Estimated Study Completion Date: 30 Dec 2025

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2023 by AstraZeneca

Collaborators

Daiichi Sankyo Company, Limited

Inclusion and exclusion criteria

Inclusion Criteria

-Patients must be at least 18 years of age
- Pathologically documented breast cancer that:
a) Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
b) 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.
c) 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
a) Disease progression on or after the last systemic therapy prior to starting study treatment
b) 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

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

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Arms	Assigned Interventions
Experimental: Module 1- T-DXd and Durvalumab T-DXd and Durvalumab	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736
Experimental: Module 2- T-DXd and Pertuzumab T-DXd and Pertuzumab	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Pertuzumab Pertuzumab: administered as an IV infusion
Experimental: Module 3- T-DXd and Paclitaxel T-DXd and Paclitaxel	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Paclitaxel Paclitaxel: administered as an IV infusion
Experimental: Module 4- T-DXd and Durvalumab and Paclitaxel T-DXd and Durvalumab and Paclitaxel	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Paclitaxel Paclitaxel: administered as an IV infusion
Experimental: Module 0- T-DXd T-DXd	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd
Experimental: Module 5 - T-DXd and Tucatanib T-DXd and tucatinib	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Tucatinib Tucatinib administered orally (tablet) twice daily Other Name: ONT-380
Experimental: Module 6 - T-DXd and Tucatinib T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Tucatinib Tucatinib administered orally (tablet) twice daily Other Name: ONT-380
Experimental: Module 7 - T-DXd T-DXd monotherapy in patients with active brain metastases (Part 2 Only)	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd

Documents available

http://BreastCancerStudyLocator.com
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

AZ Breast Cancer Study Navigators

+1-877-400-4656