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 Aug 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

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
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