Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer

Prior treatment

• Patient previously treated with any ADC targeting HER2 or TROP2
• Patients with brain metastases (BM) except for asymptomatic treated BM not requiring ongoing corticosteroid treatment with stable lesions on baseline/screening brain MRI. Patients who require treatment of brain metastases are eligible after 14 days post surgery or radiation, if felt to be clinically stable and not requiring ongoing corticosteroid treatment
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may cause misleading study interpretation or prevent completion of study procedures and followup examinations

Other illness

• Patient with uncontrolled or significant cardiovascular disease
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
• Any medical history or condition that per protocol or in the opinion of the investigator is incompatible with the study
• Patients with known allergy or severe hypersensitivity to any of the trial drugs or their excipients
• Patients with any other disease or illness that requires hospitalisation or is incompatible with the trial treatment are not eligible

Other

• Patients enrolled in another therapeutic trial within 30 days of inclusion
• Pregnant or breast-feeding women at the time of randomization or intention to become pregnant during the study and up to 7 months after treatment
• Person deprived of their liberty or under protective custody or guardianship
• Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons

• Patient must have signed a written informed consent prior to any trial specific procedures. (Note : When the patient is physically unable to give his/her written consent, a impartial witness of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent)
• Men or women ≥ 18 years of age
• Histologically confirmed metastatic or locally advanced and unresectable triple-negative breast cancer, meeting both of the following criteria by local testing:
  • HER2-low breast cancer, defined as either immunohistochemistry (IHC) 2+ / in situ hybridization (ISH)-negative or IHC 1+ (ISH-negative or untested), on either the primary or any metastatic site
  • Estrogen receptor (ER) expression \<10% and progesterone receptor (PR) expression \<10% (Note: In case of bilateral breast cancer, participation in the study is permitted as long as both tumours correspond to a triple-negative breast cancer meeting the above criteria)
• Patient eligible to receive sacituzumab-govitecan and T-Dxd according to their indication
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Women of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment for women and up to 4 months for men.
  • A woman is considered to be of childbearing potential if she is not postmenopausal or has not undergone hysterectomy. Postmenopausal is defined as any of the following:
  • Age ≥ 60 years Age \< 60 years and ≥ 12 continuous months of amenorrhea with no identified cause other than menopause Surgical sterilization (bilateral oophorectomy)
  • \- Adequate organ and bone marrow function within 28 days before enrollment. The most recent results available must be used for all parameters below:
  • Hemoglobin ≥ 9 g/dL. Red blood cell transfusion is not allowed within 1 week prior to screening assessment
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³. Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment
  • Platelet count ≥ 100,000/mm³. Platelet transfusion is not allowed within 1 week prior to registration
  • Total bilirubin ≤ 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 metastasis at baseline
  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, or \< 5 × ULN in patients with liver metastasis
  • Serum albumin ≥ 2.5 g/dL
  • Creatinine clearance (CrCl) ≥ 30 mL/min, calculated using the Cockcroft-Gault equation: CrCl (mL/min) = \[(140 - age in years) × weight in kg\] / \[72 × serum creatinine in mg/dL\] (× 0.85 for females)
• Adequate cardiac function, defined as a left ventricular ejection fraction ≥ 55% estimated by echocardiogram or multigated acquisition scintigraphy
• Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization
• Affiliated to the French Social Security System (or equivalent)
• Patient willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.