A Study of Dato-DXd With or Without Durvalumab Versus Investigator’s Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03)

Study identifier:D926XC00001

ClinicalTrials.gov identifier:NCT05629585

EudraCT identifier:2022-002680-30

CTIS identifier:N/A

Recruiting

Official Title

A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator’s Choice of Therapy in Patients with Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION-Breast03)

Medical condition

Breast Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Dato-DXd, Durvalumab, Capecitabine, Pembrolizumab

Sex

All

Estimated Enrollment

1075

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 28 Nov 2022

Estimated Primary Completion Date: 20 Sept 2027

Estimated Study Completion Date: 27 Mar 2030

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2024 by AstraZeneca

Collaborators

Daiichi Sankyo, Inc, SWOG Clinical Trials Partnerships

Inclusion and exclusion criteria

Inclusion Criteria

1. Participant must be ≥ 18 years at the time of screening.  
2. Histologically confirmed invasive TNBC, as defined by the ASCO/CAP guidelines.  
3. Residual invasive disease in the breast and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy.  
4. Completed at least 6 cycles of neoadjuvant therapy containing an anthracycline and/or a taxane with or without platinum chemotherapy, with or without pembrolizumab. 
5. No evidence of locoregional or distant relapse.  
6. Surgical removal of all clinically evident disease in the breast and lymph nodes. 
7. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation. 
8. All participants must provide an FFPE tumour sample from residual invasive disease at surgery for tissue-based analysis. 
9. No adjuvant systemic therapy. 
10. Radiotherapy (if indicated) delivered before the start of study intervention. 
11. If post-operative radiation therapy is given, an interval of no more than 6 weeks between the completion of radiation therapy and the date of randomisation (radiation therapy can be completed during screening period). If no post-operative radiation therapy is given, an interval of no more than 16 weeks between the date of breast surgery and the date of randomisation. 
12. Has LVEF ≥ 50% by either an ECHO or MUGA scan within 28 days before randomisation. 
13. Eligible for one of the therapy options listed as investigator’s choice per investigator assessment. 
14. No known germline BRCA1 or BRCA2 pathogenic mutation. 
15. Adequate bone marrow reserve and organ function within 7 days before randomisation.

Exclusion Criteria

1. Stage IV (metastatic) TNBC. 
2. History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery. 
3. Severe or uncontrolled medical conditions including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea chronic diverticulitis or previous complicated diverticulitis.
4. History of another primary malignancy except for adequately resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease (including ductal carcinoma in situ) that has undergone potentially curative therapy, or other solid malignancy treated with curative intent with no known active disease within 5 years before randomisation and of low potential risk for recurrence. 
5. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss). 
6. Active or prior documented autoimmune or inflammatory disorders.
7. Clinically significant corneal disease. 
8. Active or uncontrolled hepatitis B or C virus infection. 
9. Known HIV infection that is not well controlled
10. Active tuberculosis infection. 
11. Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening. 
12. Uncontrolled or significant cardiac disease. 
13. History of non-infectious ILD/pneumonitis including radiation, pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
14. Has severe pulmonary function compromise.
15. Any known active liver disease. 
16. Grade ≥ 2 peripheral neuropathy of any aetiology. 
17. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab. 
18. Current or prior use of immunosuppressive medication within 14 days prior to randomisation.
19. Participants with a known severe hypersensitivity to Dato-DXd or any of the excipients of these products including but not limited to polysorbate 80 or other monoclonal antibodies. 
20. Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors.
21. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to randomisation, randomisation into a prior Dato-DXd, T-DXd, or durvalumab study regardless of treatment assignment. 
22. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

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Arms	Assigned Interventions
Experimental: Dato-DXd in combination with Durvalumab Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles	Drug: Dato-DXd Experimental drug. Provided in 100mg vials. IV infusion Other Name: Datopotamab deruxtecan (Dato-DXd, DS-1062a) Drug: Durvalumab Experimental drug. Provided in 50mg vials. IV infusion Other Name: MEDI4736
Experimental: Dato-DXd Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles	Drug: Dato-DXd Experimental drug. Provided in 100mg vials. IV infusion Other Name: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Active Comparator: Investigators Choice Therapy Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab* (200 mg IV on Day 1, Q3W) for 9 cycles * Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3.	Drug: Capecitabine Active Comparator. Tablet. Oral route of administration Other Name: XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord Drug: Pembrolizumab Active Comparator. Provided in 100mg vials. IV infusion Other Name: KEYTRUDA®

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Aditya Bardia

Massachusetts General Hospital