Stage I-III triple-negative breast cancer with residual invasive disease after neoadjuvant therapy. MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Datopotamab Deruxtecan
Product Code: DS-1062a
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Datopotamab Deruxtecan
CAS Number: 2238831-60-0
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be = 18 years at the time of screening; Male or female; 2. Histologically confirmed invasive TNBC.? 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 taxane with or without carboplatin, with or without pembrolizumab. 5. No evidence of locoregional or distance relapse 6. Surgical removal of all clinically evident disease in the breast and lymph nodes 7. FFPE tumor sample from residual invasive disease at surgery 8. No adjuvant systemic therapy. Radiotherapy (if indicated) delivered before start of study treatment 9. No more than 6 weeks between completion of post-operative radiation therapy and randomization. If no post-operative radiation therapy, no more than 16 weeks between the date of breast surgery and randomization? 10. Eligible for one of the therapy options listed as ICT? 11. No known germline BRCA1 or BRCA 2 mutation 12. Adequate organ and bone marrow function; LVEF = 50% by echocardiogram or MUGA; ECOG 0 or 1? Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 537 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 538
Exclusion criteria
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. Prior anticancer therapy with topoisomerase I ADC, TROP2-targeted therapy (e.g., Trodelvy), participated in clinical studies with T-DXd? 4. Prior exposure to a PD-1/PD-L1 inhibitor other than pembrolizumab? 5. 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?; infections; active or uncontrolled HBC or HCV; HIV; active TB 6. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade =1? 7. History of ILD or severe pulmonary function compromise? 8. Clinically significant corneal disease? 9. Any known active or prior documented autoimmune or inflammatory disorders? 10. Any known active liver disease? 11. Uncontrolled or significant cardiac disease? 12. Grade =2 peripheral neuropathy of any etiology? 13. History of severe hypersensitivity to either drug substances or inactive ingredients of Dato-DXd or history of hypersensitivity to PD-1/PD-L1 inhibitors or capecitabine?
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 1. To demonstrate superiority of Dato-DXd + durvalumab relative to ICT by a) DDFS, b) OS. 2. To demonstrate superiority of Dato-DXd relative to ICT by iDFS. 3. To assess efficacy of Dato-DXd relative to ICT by a)DDFS, b) OS. 4. To assess efficacy of Dato-DXd relative to ICT by a) iDFS, b) DDFS, c) OS. 5.To assess efficacy of Dato-DXd + durvalumab relative Dato-DXd by a) iDFS, b) DDFS. 6.To assess by TTD and score levels of participant-reported a) physical function, b) QHS/QoL with Dato-DXd +/- durvalumab vs ICT. 7.To assess patient-reported fatigue Dato-DXd +/- durvalumab vs ICT. 8.To assess the a) pharmacokinetics and b) immunogenicity of Dato-Dxd. 9.To assess safety and tolerability of Dato-DXd +/- durvalumab vs ICT.;Primary end point(s): Invasive disease-free survival (iDFS) is defined as time from randomization until date of first occurrence of one of the following events: ipsilateral invasive breast tumor (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. iDFS will be determined based on disease recurrence per investigator assessment 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 HR of iDFS f | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Distant disease free survival (DDFS): defined as time from randomization to date of first distant recurrence, occurrence of second primary non-breast invasive cancer, or death from any cause. DDFS is determined based on disease recurrence per investigators assessment 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 received another anticancer therapy. The measure of interest will be the HR of DDFS for Dato-DXd + durvalumab vs. ICT. 2. DDFS for Dato-DXd vs ICT 3. DDFS for Dato-DXd + durvalumab vs Dato-DXd 4. Overall Survival (OS): defined as time from randomization until 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 received another anticancer therapy. Measure of interest will be the HR of OS for Dato-DXd + durvalumab vs ICT 5. OS for Dato-DXd vs ICT 6. iDFS for Dato-DXd vs ICT 7. iDFS for Dato-DXd + durvalumab vs ICT 8. Clinical Outcome Assessments (PRO endpoints): Time to Deterioration (TTD)and actual scores: in physical function as measured by the PROMIS Physical Function Short Form 8c and GHS/QoL as measured by the GHS/QoL scale from the EORTC IL172. The measure of interest is the HR of TTD and physical function and GHS/QoL scores for Dato-DXd +/- durvalumab vs ICT. 9. Fatigue as measured by PROMIS Fatigue Short Form 7a. The measure of interest is the proportion of participants experiencing different levels of fatigue and actual scores at 3, 6, 12 months for Dato-DXd +/- durvalumab vs ICT.Pharmacokinetics of Dato-DXd 10. Immunogenicity of Dato-DXd 11. Safety and tolerability;Timepoint(s) of evaluation of this end point: 1. 1, 2, 3, 6, 7, 8: Randomisation to event, anticipated to be up to 57 months after first subject in. 2. 4, 5: Randomisation to date of death, | — |
Countries
Argentina, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed