A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer - DB-08

Study identifier:D967JC00002

ClinicalTrials.gov identifier:NCT04556773

EudraCT identifier:2020-002797-27

CTIS identifier:2023-505690-33-00

Recruitment Complete

Official Title

A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination with Other Anti-cancer Agents in Patients with Metastatic HER2-low Breast Cancer (DESTINY-Breast08)

Medical condition

Metastatic Breast Cancer

Phase

Phase 1

Healthy volunteers

Study drug

Trastuzumab deruxtecan, Durvalumab, Paclitaxel, Capivasertib, Anastrozole, Fulvestrant, Capecitabine

Sex

All

Actual Enrollment

138

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 17 Dec 2020

Primary Completion Date: 16 Aug 2023

Estimated Study Completion Date: 28 Nov 2025

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2024 by AstraZeneca

Collaborators

Daiichi Sankyo Co., Ltd., Daiichi Sankyo Company, Limited

Inclusion and exclusion criteria

Inclusion Criteria

-Patients must be at least 18 years of age
-Male or female patients who have pathologically documented breast cancer that:
a)Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
b)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.

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.

No locations available

Arms	Assigned Interventions
Experimental: Module 1: T-DXd + capecitabine T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Capecitabine Capecitabine: administered orally Other Name: Capecitabine
Experimental: Module 2: T-DXd + durvalumab + paclitaxel 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	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 Other Name: Taxol A
Experimental: Module 3: T-DXd + capivasertib T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Capivasertib Capivasertib: administered orally Other Name: AZD5363
Experimental: Module 4: T-DXd + anastrozole T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Anastrozole Anastrozole: administered orally Other Name: Anastrozol
Experimental: Module 5: T-DXd + fulvestrant T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a, T-DXd Drug: Fulvestrant Fulvestrant: administered as an IM injection Other Name: Fulvestrant

Documents available

Download
AstraZeneca Breast Cancer Study Locator website - To learn which AstraZeneca breast cancer clinical trials are looking for participants with specific diagnosis, stage, and treatment history.
Download
redacted Study Synopsis (core + module 1-5 (combined)
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