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Comparing Dato-DXd with or without Durvalumab to standard chemotherapy for advanced triple-negative breast cancer

A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION-Breast05)

PHASE3 · AstraZeneca · NCT06103864

This study is testing if a new treatment called Dato-DXd, with or without another drug called durvalumab, can help people with advanced triple-negative breast cancer live longer without their cancer getting worse compared to standard chemotherapy.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment625 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionschemotherapy, radiation, durvalumab, pembrolizumab
Locations316 sites (Daphne, Alabama and 315 other locations)
Trial IDNCT06103864 on ClinicalTrials.gov

What this trial studies

This Phase III, randomized, open-label study evaluates the efficacy and safety of Dato-DXd, with or without durvalumab, against the standard chemotherapy regimen combined with pembrolizumab in patients with PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC). The study aims to demonstrate that the combination of Dato-DXd and durvalumab can lead to longer progression-free survival compared to standard treatments. Participants will be stratified based on geographic location, disease-free interval history, and prior PD-1/PD-L1 treatment. The study also assesses the impact of treatment on patients' quality of life.

Who should consider this trial

Good fit: Ideal candidates include individuals with PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer who have not received prior chemotherapy for their metastatic disease.

Not a fit: Patients with early-stage breast cancer or those who have previously undergone chemotherapy for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced triple-negative breast cancer, potentially leading to longer survival without disease progression.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in treating triple-negative breast cancer, indicating potential for success in this novel combination.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key 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.

Key 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.

Where this trial is running

Daphne, Alabama and 315 other locations

+266 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Breast Cancer, Triple-negative, Metastatic, Inoperable, Datopotamab deruxtecan, Dato-DXd, DS1062a, DS1062

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.