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:2019-004531-22

CTIS identifier:N/A

Recruitment Complete

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, Durvalumab, Paclitaxel, Pertuzumab, Tucatinib

Sex

All

Actual Enrollment

244

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 28 Dec 2020

Estimated Primary Completion Date: 31 Jan 2025

Estimated Study Completion Date: 02 Jul 2025

Study design

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

Verification:

Verified 01 Mar 2024 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

No locations available

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 (Arm not initiated in Part 2)	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 (Arm not initiated in Part 1 and Part 2)	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 (Arm not initiated in Part 2)	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) (Arm not initiated)	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