A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer

NCT ID: NCT06103864

Last Updated: 2026-01-12

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

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

625 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-23

Study Completion Date

2030-09-30

Brief Summary

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This is a Phase III, randomised, open-label, 3-arm, multicentre, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with investigator's choice chemotherapy in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

Detailed Description

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The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.

The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI \> 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no).

This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomised either 1:1 to Arm 1 (Dato-DXd + durvalumab) and Arm 2 (ICC + pembrolizumab), or in selected countries, 1:1:1 to Arms 1, 2 and 3 (Dato-DXd monotherapy). Once approximately 75 participants are randomised to Arm 3, this cohort will close, and all countries will continue with a 1:1 randomisation strategy for Arms 1 and 2.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dato-DXd + durvalumab

Arm 1: Dato-DXd + durvalumab

Group Type EXPERIMENTAL

Dato-DXd

Intervention Type DRUG

Provided in 100mg vials. IV infusion. Experimental drug.

Durvalumab

Intervention Type DRUG

Provided in 500mg vials. IV infusion. Experimental drug.

Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab

Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

IV infusion. Active comparator.

Nab-paclitaxel

Intervention Type DRUG

IV infusion. Active comparator.

Gemcitabine

Intervention Type DRUG

IV infusion. Active comparator.

Carboplatin

Intervention Type DRUG

IV infusion. Active comparator.

Pembrolizumab

Intervention Type DRUG

IV infusion. Active comparator.

Dato-DXd

Arm 3: Dato-DXd

Group Type EXPERIMENTAL

Dato-DXd

Intervention Type DRUG

Provided in 100mg vials. IV infusion. Experimental drug.

Interventions

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Dato-DXd

Provided in 100mg vials. IV infusion. Experimental drug.

Intervention Type DRUG

Durvalumab

Provided in 500mg vials. IV infusion. Experimental drug.

Intervention Type DRUG

Paclitaxel

IV infusion. Active comparator.

Intervention Type DRUG

Nab-paclitaxel

IV infusion. Active comparator.

Intervention Type DRUG

Gemcitabine

IV infusion. Active comparator.

Intervention Type DRUG

Carboplatin

IV infusion. Active comparator.

Intervention Type DRUG

Pembrolizumab

IV infusion. Active comparator.

Intervention Type DRUG

Other Intervention Names

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Datopotamab deruxtecan (Dato-DXd, DS-1062a) MEDI4736

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines.
* ECOG PS 0 or 1.
* Participants are expected to provide an FFPE tumour sample collected from a locally recurrent inoperable or metastatic tumour. Alternatively, an archival FFPE tumour sample can be submitted; it must have been collected ≤ 3 years prior to the participant signing informed consent (screening start).
* PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory.
* No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.

\- Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence.
* Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).
* Measurable disease as per RECIST 1.1.
* Adequate bone marrow reserve and organ function.
* Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception.

Exclusion Criteria

* As judged by investigator, any evidence of diseases (such as severe or uncontrolled medical conditions including systemic diseases, uncontrolled hypertension, serious gastrointestinal conditions associated with diarrhoea, chronic diverticulitis or previous complicated diverticulitis, history of allogeneic organ transplant, and active bleeding diseases, ongoing and active infection, significant cardiac conditions, substance abuse, psychiatric illness/social situation or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before Cycle 1 Day 1 and of low potential risk for recurrence.
* Participants with a history of previously treated neoplastic spinal cord compression or treated, clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.

\- Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.
* Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.
* Active or uncontrolled hepatitis B or C virus infection.
* Known HIV infection that is not well controlled.
* Uncontrolled or significant cardiac disease.
* History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Clinically severe pulmonary function compromise.
* Clinically significant corneal disease.
* Active or prior documented autoimmune or inflammatory disorders.
* Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.
* Any concurrent anti-cancer treatment.
* Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.
* Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Daphne, Alabama, United States

Site Status RECRUITING

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Springdale, Arkansas, United States

Site Status RECRUITING

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Duarte, California, United States

Site Status WITHDRAWN

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Glendale, California, United States

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Sacramento, California, United States

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Santa Rosa, California, United States

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Aurora, Colorado, United States

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New Haven, Connecticut, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Palm Bay, Florida, United States

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Plantation, Florida, United States

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Atlanta, Georgia, United States

Site Status SUSPENDED

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Decatur, Illinois, United States

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Elmhurst, Illinois, United States

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Naperville, Illinois, United States

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New Albany, Indiana, United States

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Des Moines, Iowa, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Louisville, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Baton Rouge, Louisiana, United States

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Baltimore, Maryland, United States

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Columbia, Maryland, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Saint Paul, Minnesota, United States

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Hattiesburg, Mississippi, United States

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St Louis, Missouri, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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New York, New York, United States

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Stony Brook, New York, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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York, Pennsylvania, United States

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Providence, Rhode Island, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Flower Mound, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Kingwood, Texas, United States

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McKinney, Texas, United States

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Sugar Land, Texas, United States

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Charlottesville, Virginia, United States

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Fairfax, Virginia, United States

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Midlothian, Virginia, United States

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Norfolk, Virginia, United States

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Roanoke, Virginia, United States

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Tacoma, Washington, United States

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Madison, Wisconsin, United States

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CABA, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Rosario, , Argentina

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San Nicolás de los Arroyos, , Argentina

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Camperdown, , Australia

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Darlinghurst, , Australia

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Heidelberg, , Australia

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Melbourne, , Australia

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Nedlands, , Australia

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Waratah, , Australia

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Barretos, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Goiânia, , Brazil

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Itajaí, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Teresina, , Brazil

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Barrie, Ontario, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Regina, Saskatchewan, Canada

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Saskatoon, Saskatchewan, Canada

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Anyang, , China

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Beijing, , China

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Beijing, , China

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Bengbu, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Chengdu, , China

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Chengdu, , China

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Chongqing, , China

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Fuzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Harbin, , China

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Hefei, , China

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Jinan, , China

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Nanchang, , China

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Nanjing, , China

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Nanjing, , China

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Nanning, , China

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Shandong, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Tianjin, , China

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Wenzhou, , China

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Wuhan, , China

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Wuhan, , China

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Xi'an, , China

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Xiamen, , China

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Xintai, , China

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Xuzhou, , China

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Zhanjiang, , China

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Zhengzhou, , China

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Zhengzhou, , China

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Lille, , France

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Lyon, , France

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Montpellier, , France

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Paris, , France

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Saint-Herblain, , France

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Toulouse, , France

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Vandœuvre-lès-Nancy, , France

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Villejuif, , France

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Düsseldorf, , Germany

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Essen, , Germany

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Georgsmarienhütte, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Heilbronn, , Germany

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Leipzig, , Germany

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

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Shatin, , Hong Kong

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Calicut, , India

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Chennai, , India

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Jaipur, , India

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Kochi, , India

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Kolkata, , India

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Marg Jaipur, , India

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Mohali, , India

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Mysuru, , India

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Nagpur, , India

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Nashik, , India

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New Delhi, , India

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New Delhi, , India

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Puducherry, , India

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Surat, , India

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Thiruvananthapuram, , India

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Vadodara, , India

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Visakhapatnam, , India

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Bergamo, , Italy

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Empoli, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Padua, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Rozzano, , Italy

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Akashi-shi, , Japan

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Bunkyō City, , Japan

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Bunkyō City, , Japan

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Chiba, , Japan

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Chūōku, , Japan

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Fukuoka, , Japan

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Fukushima, , Japan

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Gifu, , Japan

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Hidaka-shi, , Japan

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Hiroshima, , Japan

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Hiroshima, , Japan

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Isehara-shi, , Japan

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Kamogawa-shi, , Japan

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Kashiwa, , Japan

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Kitaadachi-gun, , Japan

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Kōtoku, , Japan

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Kumamoto, , Japan

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Kurume-shi, , Japan

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Matsuyama, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Niigata, , Japan

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Nishinomiya-shi, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Ota-shi, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Shinagawa-ku, , Japan

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Shinjuku-ku, , Japan

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Shinjuku-ku, , Japan

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Tsu, , Japan

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Tsukuba, , Japan

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Yokohama, , Japan

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CD Mexico, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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Mexico City, , Mexico

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México, , Mexico

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México, , Mexico

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Tuxtla Gutiérrez, , Mexico

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Bacolod, , Philippines

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Cebu City, , Philippines

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City of Muntinlupa, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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San Juan City, , Philippines

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Gdynia, , Poland

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Konin, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Legnica, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Przemyśl, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Cape Town, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Paarl, , South Africa

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Pretoria, , South Africa

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Busan, , South Korea

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Daegu, , South Korea

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Goyang-si, , South Korea

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Seongnam-si, , 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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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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Barcelona, , Spain

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Granada, , Spain

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Hospitalet deLlobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Pamplona, , Spain

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Santander, , Spain

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Hsinchu, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , 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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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

Site Status RECRUITING

Research Site

Bangkok, , Thailand

Site Status RECRUITING

Research Site

Chiang Mai, , Thailand

Site Status RECRUITING

Research Site

Dusit, , Thailand

Site Status RECRUITING

Research Site

Khon Kaen, , Thailand

Site Status RECRUITING

Research Site

Songkhla, , Thailand

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Besevler Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Istanbul, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Research Site

Izmir, , Turkey (Türkiye)

Site Status WITHDRAWN

Research Site

Küçükçekmece, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Samsun, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Cardiff, , United Kingdom

Site Status RECRUITING

Research Site

Chelsea, , United Kingdom

Site Status RECRUITING

Research Site

Leicester, , United Kingdom

Site Status RECRUITING

Research Site

Liverpool, , United Kingdom

Site Status SUSPENDED

Research Site

London, , United Kingdom

Site Status RECRUITING

Research Site

London, , United Kingdom

Site Status WITHDRAWN

Research Site

Oxford, , United Kingdom

Site Status SUSPENDED

Research Site

Surrey, , United Kingdom

Site Status SUSPENDED

Research Site

Sutton, , United Kingdom

Site Status RECRUITING

Research Site

Taunton, , United Kingdom

Site Status RECRUITING

Research Site

Da Nang, , Vietnam

Site Status NOT_YET_RECRUITING

Research Site

Hanoi, , Vietnam

Site Status RECRUITING

Research Site

Ho Chi Minh City, , Vietnam

Site Status RECRUITING

Research Site

Hồ Chí Minh, , Vietnam

Site Status RECRUITING

Research Site

Huế, , Vietnam

Site Status RECRUITING

Research Site

Việt Trì, , Vietnam

Site Status RECRUITING

Research Site

Vinh, , Vietnam

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Brazil Canada China France Germany Hong Kong India Italy Japan Mexico Philippines Poland Singapore South Africa South Korea Spain Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

AstraZeneca Breast Cancer Study Locator Service

Role: CONTACT

+1-877-400-4656

References

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Schmid P, Oliveira M, O'Shaughnessy J, Cristofanilli M, Graff SL, Im SA, Loi S, Saji S, Wang S, Cescon DW, Hovey T, Nawrot A, Tse K, Vukovic P, Curigliano G. TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer. Ther Adv Med Oncol. 2025 Apr 17;17:17588359251327992. doi: 10.1177/17588359251327992. eCollection 2025.

Reference Type DERIVED
PMID: 40297626 (View on PubMed)

Related Links

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https://www.breastcancerstudylocator.com/trial/listing/431555

Breast Cancer Study Locator details (for US)

Other Identifiers

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D7630C00001

Identifier Type: -

Identifier Source: org_study_id

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