A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer

NCT ID: NCT06112379

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

PHASE3

Total Enrollment

1902 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-14

Study Completion Date

2032-09-23

Brief Summary

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This is a Phase III, 2-arm, randomised, open-label, multicentre, global study assessing the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy compared with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer.

Detailed Description

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The primary objectives of the study are to demonstrate superiority of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy relative to neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab with or without chemotherapy in participants with previously untreated TNBC or hormone receptor-low/HER2-negative breast cancer, by investigator assessment of EFS.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomised in a 1:1 ratio to one of two intervention groups.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dato-DXd plus durvalumab

Participants receive durvalumab every 3 weeks (Q3W) + Dato-DXd Q3W as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvaluamb Q3W as adjuvant therapy post-surgery. Adjuvant chemotherapy may be given in combination with durvalumab only if participants have residual disease.

Olaparib may be given for participants with gBRCA-positive tumours and residual disease

Adjuvant chemotherapy may be one of these:

1. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) and carboplatin (weekly or Q3W) for 4 cycles (12 weeks);
2. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks);
3. Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks);
4. Capecitabine (Q3W) for 8 cycles.

Group Type EXPERIMENTAL

Dato-DXd

Intervention Type DRUG

Experimental drug IV infusion

Durvalumab

Intervention Type DRUG

Experimental drug IV Infusion

Doxorubicin

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Epirubicin

Intervention Type DRUG

IV Infusion Experimental/Active Comparator

Cyclophosphamide

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Paclitaxel

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Carboplatin

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Capecitabine

Intervention Type DRUG

Tablet Oral route of administration Experimental/Active Comparator

Olaparib

Intervention Type DRUG

Tablet Oral route of administration Experimental/Active Comparator

Pembrolizumab plus chemotherapy

Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Adjuvant capecitabine (Q3W) for 8 cycles may be given in combination with pembrolizumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

IV Infusion Active comparator

Doxorubicin

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Epirubicin

Intervention Type DRUG

IV Infusion Experimental/Active Comparator

Cyclophosphamide

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Paclitaxel

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Carboplatin

Intervention Type DRUG

IV infusion Experimental/Active Comparator

Capecitabine

Intervention Type DRUG

Tablet Oral route of administration Experimental/Active Comparator

Olaparib

Intervention Type DRUG

Tablet Oral route of administration Experimental/Active Comparator

Interventions

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Dato-DXd

Experimental drug IV infusion

Intervention Type DRUG

Durvalumab

Experimental drug IV Infusion

Intervention Type DRUG

Pembrolizumab

IV Infusion Active comparator

Intervention Type DRUG

Doxorubicin

IV infusion Experimental/Active Comparator

Intervention Type DRUG

Epirubicin

IV Infusion Experimental/Active Comparator

Intervention Type DRUG

Cyclophosphamide

IV infusion Experimental/Active Comparator

Intervention Type DRUG

Paclitaxel

IV infusion Experimental/Active Comparator

Intervention Type DRUG

Carboplatin

IV infusion Experimental/Active Comparator

Intervention Type DRUG

Capecitabine

Tablet Oral route of administration Experimental/Active Comparator

Intervention Type DRUG

Olaparib

Tablet Oral route of administration Experimental/Active Comparator

Intervention Type DRUG

Other Intervention Names

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Datopotamab deruxtecan (Dato-DXd, DS-1062a) MEDI4736 KEYTRUDA® XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord LYNPARZA®

Eligibility Criteria

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Inclusion Criteria

* Participant must be ≥ 18 years, at the time of signing the ICF.
* Histologically confirmed Stage II or III unilateral or bilateral primary invasive TNBC or hormone receptor-low/HER2-negative breast cancer
* ECOG PS of 0 or 1
* Provision of acceptable tumor sample
* Adequate bone marrow reserve and organ function
* Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and aligned with protocol requirements.

Exclusion Criteria

* History of any prior invasive breast malignancy
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 5 years before randomization.
* active or prior documented autoimmune or inflammatory disorders.
* Evidence of distant disease.
* Clinically significant corneal disease.
* Has active or uncontrolled hepatitis B or C virus infection.
* Known HIV infection that is not well controlled.
* Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections; or inability to rule out infections.
* Known to have active tuberculosis infection
* Mean resting corrected QTcF interval \> 470 ms obtained from ECG
* Uncontrolled or significant cardiac disease.
* History of non-infectious ILD/pneumonitis
* Has severe pulmonary function compromise
* Any prior or concurrent surgery, radiotherapy or systemic anticancer therapy for TNBC or hormone receptor-low/HER2-negative breast cancer
* For females only: is pregnant (confirmed with positive serum pregnancy test) or breastfeeding, or planning to become pregnant.
* Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention, or as dictated by local PI for SoC if longer.
* Concurrent use of systemic hormone replacement therapy or oral hormonal contraception
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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Daphne, Alabama, United States

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Prescott, Arizona, United States

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Jonesboro, Arkansas, United States

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Rogers, Arkansas, United States

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Los Angeles, California, United States

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Santa Barbara, California, United States

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Santa Rosa, California, United States

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Torrance, California, United States

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Aurora, Colorado, United States

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Longmont, Colorado, United States

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Bridgeport, Connecticut, United States

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New Haven, Connecticut, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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St. Petersburg, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Des Moines, Iowa, United States

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Edgewood, Kentucky, United States

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Louisville, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Annapolis, Maryland, United States

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Boston, Massachusetts, United States

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Grand Rapids, Michigan, United States

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Traverse City, Michigan, United States

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Burnsville, Minnesota, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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Omaha, Nebraska, United States

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East Brunswick, New Jersey, United States

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New Brunswick, New Jersey, United States

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Santa Fe, New Mexico, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Blue Ash, Ohio, United States

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Eugene, Oregon, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Chattanooga, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, 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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San Antonio, Texas, United States

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Webster, Texas, United States

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Fairfax, Virginia, United States

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Norfolk, Virginia, United States

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Roanoke, Virginia, United States

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Winchester, Virginia, United States

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Tacoma, Washington, United States

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East Melbourne, , Australia

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Feldkirch, , Austria

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Innsbruck, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Antwerp, , Belgium

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Brasschaat, , Belgium

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Charleroi, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Libramont-Chevigny, , Belgium

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Brasília, , Brazil

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Londrina, , 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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Ribeirão Preto, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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Taubaté, , Brazil

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Vitória, , Brazil

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Shumen, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Barrie, Ontario, Canada

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London, Ontario, Canada

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Oshawa, Ontario, Canada

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Toronto, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Saint-Jérôme, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Montreal, , Canada

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Ottawa, , Canada

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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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Chengdu, , 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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Harbin, , China

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Jinan, , China

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Linhai, , China

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Nanchang, , China

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Nanchang, , China

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Nanjing, , China

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Nanning, , China

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Shanghai, , China

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Shenyang, , China

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Shijiazhuang, , China

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Suining, , China

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Tianjin, , China

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Wuhan, , China

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Xi'an, , China

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Xintai, , China

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Zhaoqing, , China

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Zhengzhou, , China

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Avignon, , France

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Bayonne, , France

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Caen, , France

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Clermont-Ferrand, , France

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Limoges, , France

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Marseille, , France

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Montpellier, , France

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Nice, , France

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Paris, , France

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Reims, , 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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Augsburg, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Dessau, , Germany

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Dresden, , Germany

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Erlangen, , Germany

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Essen, , Germany

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Esslingen am Neckar, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Kiel, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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München, , Germany

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Münster, , Germany

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Trier, , Germany

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Ulm, , Germany

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Hong Kong, , Hong Kong

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Budapest, , Hungary

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Kecskemét, , Hungary

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Miskolc, , Hungary

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Szekszárd, , Hungary

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Bengaluru, , India

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Delhi, , India

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Delhi, , India

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Kolkata, , India

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Kolkata, , India

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Marg Jaipur, , India

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Nagpur, , India

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Nashik, , India

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Thiruvananthapuram, , India

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Vadodara, , India

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Empoli, , Italy

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Lucca, , Italy

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Macerata, , 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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Roma, , Italy

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Rozzano, , Italy

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Torino, , Italy

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Tricase, , Italy

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Udine, , Italy

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Akashi-shi, , Japan

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Akita, , Japan

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Bunkyō City, , Japan

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Chiba, , Japan

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Chūōku, , 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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Hirakata-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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Kashiwa, , Japan

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Kumamoto, , Japan

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Kurume-shi, , Japan

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Kyoto, , Japan

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Matsuyama, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Sapporo, , 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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Sunto-gun, , Japan

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Tsu, , Japan

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Yokohama, , Japan

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George Town, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Selangor, , Malaysia

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Kuching, , Malaysia

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Singapore, , Singapore

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Daegu, , South Korea

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Goyang-si, , South Korea

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Seongnam, , 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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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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Santiago de Compostela, , Spain

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Seville, , Spain

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Zaragoza, , Spain

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Baden, , Switzerland

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Basel, , Switzerland

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Bern, , Switzerland

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Frauenfeld, , Switzerland

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Changhua, , 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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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Dusit, , Thailand

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Muang, , Thailand

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Songkhla, , Thailand

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Adapazarı, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Samsun, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Cardiff, , United Kingdom

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Lancaster, , United Kingdom

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London, , United Kingdom

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Northampton, , United Kingdom

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Oxford, , United Kingdom

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Taunton, , United Kingdom

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Hồ Chí Minh, , Vietnam

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Vinh, , Vietnam

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Countries

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United States Australia Austria Belgium Brazil Bulgaria Canada China France Germany Hong Kong Hungary India Italy Japan Malaysia Poland Singapore South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

References

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McArthur HL, Tolaney SM, Dent R, Schmid P, Asselah J, Liu Q, Meisel JL, Niikura N, Park YH, Werutsky G, Bianchini G, Andersen JC, Kozarski R, Rokutanda N, Pistilli B, Loibl S. TROPION-Breast04: a randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naive early-stage triple negative or HR-low/HER2- breast cancer. Ther Adv Med Oncol. 2025 Feb 5;17:17588359251316176. doi: 10.1177/17588359251316176. eCollection 2025.

Reference Type DERIVED
PMID: 39917260 (View on PubMed)

Related Links

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https://www.breastcancerstudylocator.com/trial/listing/432775

Breast Cancer Study Locator details (for US)

Other Identifiers

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2023-505928-59-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

D926QC00001

Identifier Type: -

Identifier Source: org_study_id