Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Datopotamab deruxtecan: 6.0 mg/kg IV on Day 1, Q3W
Control Intervention1: Investigator Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel, Capecitabine, Eribulin mesylate, Carboplatin):
choice between the 2 doses will be determined by standard institutional practice.
Eribulin mesylate (1.4 mg/m2 IV on Day 1 and Day 8, Q3W)
Carboplatin (area under the curve [AUC] 6 [using Calvert form
Sponsors
AstraZeneca Pharma India Ltd
AstraZeneca AB
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1. Participant must be = 18 years (= 20 years in Japan) at the time of screening. 2. Histologically or cytologically documented locally recurrent inoperable or metastatic TNBC. TNBC is defined as: Negative for ER with Negative for progesterone receptor with Negative for HER2 with 0 or 1+ intensity on IHC or 2+ intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guideline 3. No prior chemotherapy or targeted systemic therapy for metastatic or locally recurrent inoperable breast cancer. 4. Not a candidate for PD-1/PD-L1 inhibitor therapy, defined as: Participants whose tumours are PD-L1-negative, or Participants whose tumours are PD-L1-positive and have: 1) relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer, 2) comorbidities precluding PD-1/PD-L1 inhibitor therapy, or 3) no regulatory access to pembrolizumab [participant’s country does not have regulatory approval at the time of screening]). 5. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements. 6. ECOG PS 0 or 1 7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), per investigator assessment. 8. Has had an adequate treatment washout period before Cycle 1 Day 1 9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation. 10. Participants with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy. 11. Adequate organ and bone marrow function within 7 days before day of first dosing . Haemoglobin = 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment). Absolute neutrophil count = 1.5 × 109/L (granulocyte colony-stimulating factor administration is not allowed within 1 week prior to screening assessment). Platelet count = 100 × 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment). Total bilirubin (TBL) = 1.5 × upper limit of normal (ULN) if no liver metastases or Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN for AST/ALT ( Calculated CrCL = 30 mL/minute as determined by Cockcroft-Gault (using actual body weight) 12. Minimum life expectancy of 12 weeks.
Exclusion criteria
Exclusion criteria: Inclusion criteria: 1. Participant must be = 18 years (= 20 years in Japan) at the time of screening. 2. Histologically or cytologically documented locally recurrent inoperable or metastatic TNBC. TNBC is defined as: Negative for ER with Negative for progesterone receptor with Negative for HER2 with 0 or 1+ intensity on IHC or 2+ intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guideline 3. No prior chemotherapy or targeted systemic therapy for metastatic or locally recurrent inoperable breast cancer. 4. Not a candidate for PD-1/PD-L1 inhibitor therapy, defined as: Participants whose tumours are PD-L1-negative, or Participants whose tumours are PD-L1-positive and have: 1) relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer, 2) comorbidities precluding PD-1/PD-L1 inhibitor therapy, or 3) no regulatory access to pembrolizumab [participant’s country does not have regulatory approval at the time of screening]). 5. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements. 6. ECOG PS 0 or 1 7. Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), per investigator assessment. 8. Has had an adequate treatment washout period before Cycle 1 Day 1 9. Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation. 10. Participants with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy. 11. Adequate organ and bone marrow function within 7 days before day of first dosing . Haemoglobin = 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment). Absolute neutrophil count = 1.5 × 109/L (granulocyte colony-stimulating factor administration is not allowed within 1 week prior to screening assessment). Platelet count = 100 × 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment). Total bilirubin (TBL) = 1.5 × upper limit of normal (ULN) if no liver metastases or Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN for AST/ALT ( Calculated CrCL = 30 mL/minute as determined by Cockcroft-Gault (using actual body weight) 12. Minimum life expectancy of 12 weeks. Exclusion criteria: Medical Conditions 1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Radiological Progression-Free Survival (PFS) - time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first & Overall Survival (OS)-time from randomization to death from any cause Timepoint: For PFS, From Randomization Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression. For OS, every 3 months ± 14 days following objective PD or treatment discontinuation until the end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) Timepoint: Data obtained from randomisation up until progression (Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression.);Duration of response (DOR)Timepoint: Every 6 weeks (± 7 days) from randomisation for 48 weeks, then every 9 weeks (±7 days) thereafter until RECIST 1.1 disease progression;Disease control rate (DCR)Timepoint: At 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD, per RECIST 1.1 From randomisation up until progression.;Time to deterioration (TTD)Timepoint: From Randomization to deterioration or End of study at each patient visit.;Time to second progression or death (PFS2)Timepoint: Following objective progression that is confirmed by investigator assessment, participants will have their subsequent progression status recorded every 3 months (± 14 days) per local standard clinical practice to assess PFS2.;Time to Second Subsequent Therapy (TSST)Timepoint: From randomisation to (each patient visit per protocol) until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause. | — |
Countries
Afghanistan, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Mexico, Philippines, Poland, Republic of Korea, Russian Federation, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd.
Outcome results
None listed