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)

Plain English Summary

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 is a Phase 3 clinical trial sponsored by AstraZeneca studying Breast Cancer. This trial tests a new combination of drugs, datopotamab deruxtecan (Dato-DXd) with durvalumab, against a standard treatment (pembrolizumab with chemotherapy) for early-stage breast cancer. It is for adults with previously untreated triple-negative breast cancer (TNBC) or hormone receptor-low/HER2-negative breast cancer. Participants will receive either the new drug combination or the standard treatment before surgery, followed by additional treatment after surgery. The main alternative is the standard treatment arm of the trial, which involves pembrolizumab plus chemotherapy. The trial aims to enroll 1902 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older and have been diagnosed with Stage II or III triple-negative breast cancer or hormone receptor-low/HER2-negative breast cancer that has not been previously treated. You cannot join if you have a history of other breast cancers, certain other cancers treated within the last 5 years, autoimmune diseases, distant cancer spread, or significant heart or lung conditions. You must have a good general health status (ECOG PS 0 or 1) and adequate organ function. Women who are pregnant or breastfeeding cannot participate. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome, Event-Free Survival (EFS), measures how long patients live without their cancer returning or progressing, indicating how well the treatment prevents the cancer from coming back. The specific primary outcome measures are: Event-free survival (EFS) in the experimental vs control arms (Date of randomization to date of the EFS event, up to 93 months after the first subject randomized). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to find a more effective treatment for a specific type of early-stage breast cancer that has limited treatment options, potentially improving outcomes for patients. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial is testing a novel combination therapy in a large patient population for a significant unmet need in breast cancer, suggesting a potential for market entry if successful. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1902 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, the potential benefits and risks of each treatment arm, and what participation involves on a day-to-day basis. Participation involves receiving study drugs before and after surgery, with regular clinic visits for assessments and monitoring. Be prepared for potential side effects and the need for close medical supervision throughout the study. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,902 participants

Interventions

• DRUG: Dato-DXd — Experimental drug IV infusion
• DRUG: Durvalumab — Experimental drug IV Infusion
• DRUG: Pembrolizumab — IV Infusion Active comparator
• DRUG: Doxorubicin — IV infusion Experimental/Active Comparator
• DRUG: Epirubicin — IV Infusion Experimental/Active Comparator

Primary Outcomes

• Event-free survival (EFS) in the experimental vs control arms (Date of randomization to date of the EFS event, up to 93 months after the first subject randomized)

Secondary Outcomes

• Pathologic Complete Response (pCR) in the experimental vs control arms (At the time of definitive surgery)
• Overall Survival (OS) in the experimental vs control arms (Date of randomization to date of death due to any cause, up to 108 months after the first subject randomized)
• Distant disease-free survival (DDFS) in the experimental vs control arms (Date of randomization to date of the DDFS event, up to 93 months after the first subject randomized)
• Participant-reported breast and arm symptoms in the experimental vs. control arms (From Cycle 1 Day 1 of neoadjuvant treatment until pre-surgery safety FU visit (for approximately 24 weeks) or EOT - whichever occurs first.)
• Participant-reported physical function in the experimental vs. control arms (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).)

Full Eligibility Criteria

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

Trial Locations

• Research Site, Daphne, Alabama, United States
• Research Site, Prescott, Arizona, United States
• Research Site, Jonesboro, Arkansas, United States
• Research Site, Rogers, Arkansas, United States
• Research Site, Los Angeles, California, United States
• Research Site, Santa Barbara, California, United States
• Research Site, Santa Rosa, California, United States
• Research Site, Torrance, California, United States
• Research Site, Aurora, Colorado, United States
• Research Site, Longmont, Colorado, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Triple-Negative Breast Cancer
• Hormone Receptor-Low Breast Cancer
• HER2-Negative Breast Cancer
• Early-Stage Breast Cancer
• Neoadjuvant Therapy
• Adjuvant Therapy
• Oncology
• Immunotherapy
• Targeted Therapy

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