A Study of Dato-DXd Versus Investigators Choice Chemotherapy in Patientswith Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, who are not Candidates for PD-1/PD-L1 Inhibitor Therapy

Phase 3

Conditions: Health Condition 1: C509- Malignant neoplasm of breast of unspecified site

Registration Number: CTRI/2022/10/046630

Lead Sponsor: AstraZeneca Pharma India Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Yet Recruiting

Sex: Not specified

Target Recruitment: 0

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 < 1% of tumour cells positive for ER on IHC.

Negative for progesterone receptor with < 1% of tumour cells positive for progesterone receptor on IHC.

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 < 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN for AST/ALT ( < 5 × ULN in participants with liver metastases).

Calculated CrCL = 30 mL/minute as determined by Cockcroft-Gault (using actual body weight)

12. Minimum life expectancy of 12 weeks.

Exclusion Criteria

Inclusion criteria: