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

Metastatic Breast Cancer Clinical Trial

— DB-08  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04556773
• Other study ID #: D967JC00002
• Secondary ID: 2023-505690-33-0
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 17, 2020
• Est. completion date: November 28, 2025

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

Description:

This study is modular in design allowing assessment of the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the Part 2 dose-expansion phase will use the RP2D determined in Part 1.

The target population of interest in this study is patients with HER2-low (IHC 1+ or IHC 2+/ISH -) (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally confirmed HER2-low advanced/MBC in second-line or later (≥ 2L) settings

Part 2 of each module will enroll patients with HER2-low MBC who have either not received prior treatment, or received only 1 prior treatment (depending on the module-specific exclusion criteria) for advanced/metastatic disease

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: November 28, 2025
• Est. primary completion date: August 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patients must be at least 18 years of age

• Male or female patients who have pathologically documented breast cancer that:

1. Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay

2. 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.

Key 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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
• Durvalumab
Durvalumab: administered as an IV infusion
• Paclitaxel
Paclitaxel: administered as an IV infusion
• Capivasertib
Capivasertib: administered orally
• Anastrozole
Anastrozole: administered orally
• Fulvestrant
Fulvestrant: administered as an IM injection
• Capecitabine
Capecitabine: administered orally

Locations

Country	Name	City	State
Australia	Research Site	East Melbourne
Australia	Research Site	Westmead
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Belgium	Research Site	Ottignies
Brazil	Research Site	Goiania
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Quebec
France	Research Site	Villejuif Cedex
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Monterrey
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Commack	New York
United States	Research Site	Fort Worth	Texas
United States	Research Site	Germantown	Tennessee
United States	Research Site	Harrison	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Uniondale	New York

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo Co., Ltd., Daiichi Sankyo Company, Limited

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  France,  Korea, Republic of,  Mexico,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of adverse events (AEs)- Part 1	Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 24 months
Primary	Occurrence of serious adverse events (SAEs)- Part 1	Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 24 months
Primary	Occurrence of adverse events (AEs)- Part 2	Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 24 months
Primary	Occurrence of serious adverse events (SAEs)- Part 2	Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 24 months
Secondary	Objective Response Rate (ORR)- Part 2	ORR defined as the proportion of patients who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1	Until progression, assessed up to approximately 24 months
Secondary	Progression Free Survival (PFS)- Part 2	PFS defined as time from the date of first dose until the date of progression as determined by the investigator at local site per RECIST 1.1, or death due to any cause	Until progression or death, assessed up to approximately 24 months
Secondary	Duration of Response (DoR)- Part 2	DoR defined as time from the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression	Until progression or death, assessed up to approximately 24 months
Secondary	Overall Survival (OS)- Part 2	OS defined as time from the date of first dose until the date of death by any cause	Until death, assessed up to approximately 24 months
Secondary	Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a	Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration	While on study drug up to study completion, approximately 24 months
Secondary	Immunogenicity of trastuzumab deruxtecan	Percentage of patients who develop ADA for trastuzumab deruxtecan	Up to follow-up period, approximately 24 months
Secondary	Serum Concentration of durvalumab	Determination of durvalumab concentration in serum at different time points after administration	While on study drug up to study completion, approximately 24 months
Secondary	Immunogenicity of durvalumab	Percentage of patients who develop ADAs for durvalumab	Up to follow-up period, approximately 24 months

External Links

•   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.