Purpose

This is a Phase III, randomized, open-label, 3-arm, multicenter, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with ICT in participants with stage I to III TNBC with residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy.

Condition

Eligibility

Eligible Ages
Between 18 Years and 130 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Parallel
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • Datopotamab deruxtecan (Dato-DXd, DS-1062a)
  • Drug: Durvalumab
    Experimental drug. Provided in 50mg vials. IV infusion
    Other names:
    • 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 names:
    • Datopotamab deruxtecan (Dato-DXd, DS-1062a)
  • Drug: Durvalumab
    Experimental drug. Provided in 50mg vials. IV infusion
    Other names:
    • MEDI4736
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 names:
    • XELODA®, Capecitabine Cell Pharm, Capecitabine EG, Capecitabine Accord
  • Drug: Pembrolizumab
    Active Comparator. Provided in 100mg vials. IV infusion
    Other names:
    • KEYTRUDA®

Recruiting Locations

Research Site
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

The study will investigate the efficacy and safety of Dato-DXd with or without durvalumab when compared with ICT (capecitabine and/or pembrolizumab) in participants with stage I to III TNBC who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy. The primary objective of the study is to demonstrate superiority of Dato-DXd in combination with durvalumab relative to ICT by assessment of iDFS in participants with stage I to III TNBC with residual invasive disease at surgical resection following neoadjuvant therapy.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.