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NCT Number: NCT06112379

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, East Melbourne, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dato-DXd

Drug

Experimental drug IV infusion

Other names: Datopotamab deruxtecan (Dato-DXd, DS-1062a)

Durvalumab

Drug

Experimental drug IV Infusion

Other names: MEDI4736

Pembrolizumab

Drug

IV Infusion Active comparator

Other names: KEYTRUDA®

Doxorubicin

Drug

IV infusion Experimental/Active Comparator

Epirubicin

Drug

IV Infusion Experimental/Active Comparator

Cyclophosphamide

Drug

IV infusion Experimental/Active Comparator

paclitaxel

Drug

IV infusion Experimental/Active Comparator

carboplatin

Drug

IV infusion Experimental/Active Comparator

Capecitabine

Drug

Tablet Oral route of administration Experimental/Active Comparator

Other names: XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord

Olaparib

Drug

Tablet Oral route of administration Experimental/Active Comparator

Other names: LYNPARZA®

Primary outcomes

  1. Event-free survival (EFS) in the experimental vs control arms

    Time frame: Date of randomization to date of the EFS event, up to 93 months after the first subject randomized

    EFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary invasive cancer (other than squamous or basal cell skin cancer), or relapse from prior malignancy, or death by any cause (in the absence of recurrence). Non-invasive breast cancers and positive margins in the surgical sample do not count as an event for EFS. EFS will be determined by the investigator based on all available clinical assessments.

    The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest will be the Hazard Ratio of EFS.

Secondary outcomes

  1. Pathologic Complete Response (pCR) in the experimental vs control arms

    Time frame: At the time of definitive surgery

    pCR rate is defined as the proportion of participants who have no evidence by haematoxylin and eosin staining of residual invasive disease or lymphovascular invasion at the time of definitive surgery in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by blinded central evaluation.

    The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest will be the difference between the pCR rates.

  2. Overall Survival (OS) in the experimental vs control arms

    Time frame: Date of randomization to date of death due to any cause, up to 108 months after the first subject randomized

    Key Secondary - OS is defined as the time from the date of randomisation until the date of death due to any cause.

    The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest will be the Hazard Ratio of OS.

  3. Distant disease-free survival (DDFS) in the experimental vs control arms

    Time frame: Date of randomization to date of the DDFS event, up to 93 months after the first subject randomized

    DDFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: distant metastasis, occurrence of second primary invasive cancer (other than squamous or basal cell skin cancer), relapse from prior malignancy or death by any cause (in the absence of recurrence). DDFS will be determined by the investigator based on all available clinical assessments.

    The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest will be the Hazard Ratio of DDFS.

  4. Participant-reported breast and arm symptoms in the experimental vs. control arms

    Time frame: From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first.

    Breast and arm symptoms measured by the EORTC IL116. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest is the mean between-arm difference in breast and arm symptom scores.

  5. Participant-reported physical function in the experimental vs. control arms

    Time frame: From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).

    Physical function measured by the PROMIS Physical Function Short Form 8c. The analysis will include all dosed participants. The measure of interest is the mean between-arm difference in physical function scores.

  6. Participant-reported fatigue in the experimental vs. control arms

    Time frame: From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).

    Fatigue measured by the PROMIS Fatigue Short Form 7a. The analysis will include all dosed participants. The measure of interest will be the difference on the proportions of participants reporting different levels of fatigue and mean between-arm difference in the fatigue scores.

  7. Participant-reported Global health status/Quality of life (GHS/QoL)in the experimental vs. control arms

    Time frame: From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first, and then from Cycle 1 Day 1 of adjuvant treatment until EOT (for approximately 27 weeks).

    Global health status/Quality of life measured by EORTC IL172. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy.

    The measure of interest is the mean between-arm difference in GHS/QoL scores.

  8. Pharmacokinetics of Dato-DXd (in combination with durvalumab)

    Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit

    Plasma concentrations of Dato-DXd (ug/ml )

  9. Pharmacokinetics of Dato-DXd (in combination with durvalumab)

    Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit

    Plasma concentrations of total anti-TROP2 antibody (ug/ml )

  10. Pharmacokinetics of Dato-DXd (in combination with durvalumab)

    Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit

    Plasma concentrations of DXd (MAAA-1181a) (ng/ml)

  11. Immunogenicity of Dato-DXd (in combination with durvalumab)

    Time frame: Day 1 of cycles 1,2,4,8 (Each cycle is 21 days) and at pre-surgery safety follow up visit

    Presence of antidrug antibodies (ADAs) for Dato-DXd (confirmatory results: positive or negative, titres).

  12. Safety of Dato-DXd (in combination with durvalumab)

    Time frame: Randomization to final safety follow-up visit, either 90 days after last dose of study intervention for those who complete planned study intervention or 90 days after date of discontinuation for those who discontinue study intervention prematurely

    Safety and tolerability will be evaluated in terms of AEs graded by CTCAE version 5.0

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Daiichi Sankyo

Registry information

Official study title

A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (D926QC00001; TROPION-Breast04)

Important dates

Study start
2023
Primary completion
2028
Study completion
2032
First posted
Nov 1, 2023
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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