A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer

NCT ID: NCT04538742

Last Updated: 2025-12-08

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/PHASE2

Total Enrollment

245 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-28

Study Completion Date

2030-01-31

Brief Summary

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DESTINY-Breast07 will investigate 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

Detailed Description

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

The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Conditions

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Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

The study will consist of 2 phases: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later.Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Module 1- T-DXd and Durvalumab

T-DXd and Durvalumab

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Durvalumab

Intervention Type DRUG

Durvalumab: administered as an IV infusion

Module 2- T-DXd and Pertuzumab

T-DXd and Pertuzumab

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Pertuzumab

Intervention Type DRUG

Pertuzumab: administered as an IV infusion

Module 3- T-DXd and Paclitaxel

T-DXd and Paclitaxel (Arm not initiated in Part 2)

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Paclitaxel

Intervention Type DRUG

Paclitaxel: administered as an IV infusion

Module 4- T-DXd and Durvalumab and Paclitaxel

T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2)

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Durvalumab

Intervention Type DRUG

Durvalumab: administered as an IV infusion

Paclitaxel

Intervention Type DRUG

Paclitaxel: administered as an IV infusion

Module 0- T-DXd

T-DXd

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Module 5 - T-DXd and Tucatanib

T-DXd and tucatinib (Arm not initiated in Part 2)

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Tucatinib

Intervention Type DRUG

Tucatinib administered orally (tablet) twice daily

Module 6 - T-DXd and Tucatinib

T-DXd and tucatinib in patients with active brain metastases (Part 2 Only) (Arm not initiated)

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Tucatinib

Intervention Type DRUG

Tucatinib administered orally (tablet) twice daily

Module 7 - T-DXd

T-DXd monotherapy in patients with active brain metastases (Part 2 Only)

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Interventions

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Trastuzumab deruxtecan

T-DXd: administered as an IV infusion

Intervention Type DRUG

Durvalumab

Durvalumab: administered as an IV infusion

Intervention Type DRUG

Paclitaxel

Paclitaxel: administered as an IV infusion

Intervention Type DRUG

Pertuzumab

Pertuzumab: administered as an IV infusion

Intervention Type DRUG

Tucatinib

Tucatinib administered orally (tablet) twice daily

Intervention Type DRUG

Other Intervention Names

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DS-8201a, T-DXd MEDI4736 ONT-380

Eligibility Criteria

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Inclusion Criteria

* Patients must be at least 18 years of age
* Pathologically documented breast cancer that:

1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
2. 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.
3. 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

1. Disease progression on or after the last systemic therapy prior to starting study treatment
2. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Daiichi Sankyo Company, Limited

UNKNOWN

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Fort Myers, Florida, United States

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St. Petersburg, Florida, United States

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Commack, New York, United States

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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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Columbus, Ohio, United States

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Nashville, Tennessee, United States

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Fort Worth, Texas, United States

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Fairfax, Virginia, United States

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Melbourne, , Australia

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Barretos, , Brazil

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Belo Horizonte, , Brazil

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Natal, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Sorocaba, , Brazil

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Toronto, , Canada

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Villejuif, , France

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München, , Germany

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Würzburg, , Germany

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Delhi, , India

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Gurgaon, , India

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Madurai, , India

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Mumbai, , India

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Bologna, , Italy

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Milan, , Italy

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Napoli, , Italy

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Rome, , Italy

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Bydgoszcz, , Poland

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Koszalin, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Busan, , 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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Seoul, , South Korea

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Hualien City, , Taiwan

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Tainan, , 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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Taipei, , Taiwan

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Taoyuan, , Taiwan

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Ankara, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Buckhurst Hill, , United Kingdom

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Countries

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United States Australia Brazil Canada France Germany India Italy Poland Russia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Related Links

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Other Identifiers

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2023-505309-18-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-004531-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D967JC00001

Identifier Type: -

Identifier Source: org_study_id

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