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

NCT ID: NCT04556773

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-17

Study Completion Date

2026-06-16

Brief Summary

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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

Detailed Description

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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

Conditions

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Metastatic Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

The study will initially consist of 5 treatment modules, each of which includes T-DXd in combination with other anti-cancer agents. Each module 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 recommended Phase 2 dose (RP2D) for the combination, either as determined in Part 1 or from another clinical study if appropriate. For each module, patients will be centrally assigned to one of the open modules, as per the module specific criteria.

In addition to safety and tolerability, this study will also assess ORR, PFS, DoR, and OS for each treatment combination.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Module 1: T-DXd + capecitabine

T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

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

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

Paclitaxel: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Durvalumab

Intervention Type DRUG

Durvalumab: administered as an IV infusion

Module 3: T-DXd + capivasertib

T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use

Group Type EXPERIMENTAL

Capivasertib

Intervention Type DRUG

Capivasertib: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Module 4: T-DXd + anastrozole

T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral

Group Type EXPERIMENTAL

Anastrozole

Intervention Type DRUG

Anastrozole: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Module 5: T-DXd + fulvestrant

T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

Fulvestrant: administered as an IM injection

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Interventions

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Fulvestrant

Fulvestrant: administered as an IM injection

Intervention Type DRUG

Capecitabine

Capecitabine: administered orally

Intervention Type DRUG

Anastrozole

Anastrozole: administered orally

Intervention Type DRUG

Paclitaxel

Paclitaxel: administered as an IV infusion

Intervention Type DRUG

Capivasertib

Capivasertib: administered orally

Intervention Type DRUG

Trastuzumab deruxtecan

T-DXd: administered as an IV infusion

Intervention Type DRUG

Durvalumab

Durvalumab: administered as an IV infusion

Intervention Type DRUG

Other Intervention Names

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DS-8201a, T-DXd MEDI4736 Taxol A AZD5363 Anastrozol

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo Company, Limited

UNKNOWN

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Komal Jhaveri, MD, FACP

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Research Site

Commack, New York, United States

Site Status

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Harrison, New York, United States

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New York, New York, United States

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New York, New York, United States

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Uniondale, New York, United States

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Chapel Hill, North Carolina, United States

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Chattanooga, Tennessee, United States

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Germantown, Tennessee, United States

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Fort Worth, Texas, United States

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East Melbourne, , Australia

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Westmead, , Australia

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Edegem, , Belgium

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Leuven, , Belgium

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Ottignies, , Belgium

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Goiânia, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Kelowna, British Columbia, Canada

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Québec, Quebec, Canada

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Villejuif, , France

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Monterrey, , Mexico

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

Site Status

Countries

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United States Australia Belgium Brazil Canada France Mexico Russia South Korea Taiwan

Related Links

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http://BreastCancerStudyLocator.com

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.

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D967JC00002&amp;attachmentIdentifier=c690e364-5c63-4c87-b881-d6402fd48581&amp;fileName=d967jc00002-study-synopsis-core,_module_1-5_(combined)_-_redacted.pdf&amp;versionIdentifier=

redacted Study Synopsis (core + module 1-5 (combined)

Other Identifiers

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2023-505690-33-00

Identifier Type: OTHER

Identifier Source: secondary_id

2020-002797-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D967JC00002

Identifier Type: -

Identifier Source: org_study_id