TROPION-Breast02

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

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]).

Has had an adequate treatment washout period before Cycle 1 Day 1, defined as:

• Major surgery: ≥ 3 weeks.
• Radiation therapy including palliative radiation to chest: ≥ 4 weeks (palliative radiation therapy to other areas ≥ 2 weeks).
• Corticosteroid therapy for central nervous system metastatic disease: > 3 days.
• Anti cancer therapy including hormonal therapy: ≥ 3 weeks (for small molecule targeted agents: ≥ 2 weeks or 5 half-lives, whichever is longer).
• Antibody-based anti cancer therapy: ≥ 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases).
• Chloroquine/hydroxychloroquine: > 14 days.

Adequate organ and bone marrow function within 7 days before day of first dosing as follows:

• 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 × 10^9/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment).
• Platelet count ≥ 100 × 10^9/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
• International normalised ratio (INR) or prothrombin time, and either partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT): ≤ 1.5 × ULN.

Minimum life expectancy of 12 weeks.

Sex

Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Reproduction

Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or use an acceptable method of contraception from the time of screening throughout the total duration of the study and the drug washout period (at least 4 months after the last dose of study intervention) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and drug washout period is an acceptable practice, if this is the preferred usual lifestyle of the participant. Periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Informed Consent