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)

JRCT ID: jRCT2061220087

Registered date:22/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Breast Cancer
• Date of first enrollment: 24/03/2023
• Target sample size: 1075
• Countries of recruitment: Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Germany,Japan,Korea,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles
Arm 2: Dato-DXd 6 mg/kg IV Q3W x 8 cycles
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.

Outcome(s)

• Primary Outcome: Invasive disease-free survival (iDFS) for Dato-DXd + durvalumab vs. ICT [ Time Frame: From randomization until recurrence as assessed by investigator or death due to any cause up to 57 months from first subject in ]

Secondary Outcome

Distant disease-free survival (DDFS) for Dato-DXd + durvalumab vs ICT
DDFS for Dato-DXd vs ICT
DDFS for Dato-DXd + durvalumab vs Dato-DXd
Overall Survival (OS) for Dato-DXd + durvalumab vs ICT
OS for Dato-DXd vs ICT
iDFS for Dato-DXd vs ICT
iDFS for Dato-DXd + durvalumab vs Dato-DXd
Time to Deterioration (TTD) in physical functioning in participants treated with Dato-DXd with or without durvalumab compared with ICT
Participant-reported in GHS/QoL in participants treated with Dato-DXd with or without durvalumab compared with ICT
Participant-reported fatigue in participants treated with Dato-DXd with or without durvalumab compared with ICT
Pharmacokinetics of Dato-DXd
Immunogenicity of Dato-DXd
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 130age old
• Gender: Both

Include criteria

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

Exclude criteria

Stage IV (metastatic) TNBC.
History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.
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.
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.
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).
Active or prior documented autoimmune or inflammatory disorders.
Clinically significant corneal disease.
Active or uncontrolled hepatitis B or C virus infection.
Known HIV infection that is not well controlled.
Active tuberculosis infection.
Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening.
Uncontrolled or significant cardiac disease.
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.
Has severe pulmonary function compromise.
Any known active liver disease.
Grade >= 2 peripheral neuropathy of any aetiology.
Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab.
Current or prior use of immunosuppressive medication within 14 days prior to randomisation.
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.
Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors.
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.
Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT05629585