TRASTUZUMAB DERUXTECAN for Triple-negative breast cancer (HER2-low), metastatic or locally advanced

Inclusion criteria

• {"criterion_text":"- Patient must have signed a written informed consent prior to any trial specific procedures.\n- Affiliated to the French Social Security System (or equivalent).\n- 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.\n- Men or women ≥ 18 years of age;\n- Histologically confirmed metastatic or locally advanced and unresectable triple negative breast cancer that meets both of the following criteria by local testing: • HER2-low breast cancer (BC) with documented evidence of HER2-low defined as: [immunohistochemistry (IHC) 2+/in situ hybridization (ISH)- or IHC 1+ (ISH- or untested)] on either the primary or any metastatic site • With Estrogen Receptor expression <10% AND Progesterone Receptor expression <10%,\n- Patient eligible to receive sacituzumab-govitecan and T-Dxd according to their indication\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤1\n- Woman 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 the study treatment for women and up to 4 months for men..\n- Adequate organ and bone marrow functions within 28 days before enrollment. For all parameters listed below, the most recent results available must be used • Hemoglobin ≥ 9 g/dL. Note: Red blood cell transfusion is not allowed within 1 week prior to screening assessment. • Absolute neutrophil count (ANC) ≥ 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment. • Platelet count ≥ 100,000/mm3. Note: 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 and Gault equation). Cockcroft-Gault equation: CrCl (mL/min) = [140 - age (years)] × weight (kg) 72 × serum creatinine (mg/dL) {× 0.85 for females}.\n- Adequate cardiac function, defined as a left ventricular ejection fraction ≥ 55% estimated by echocardiogram or multigated acquisition scintigraphy.\n- Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization."}

Exclusion criteria

• {"criterion_text":"- Previously treated with any ADC targeting HER2 or TROP2\n- Uncontrolled or significant cardiovascular disease\n- 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\n- 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\n- Any medical history or condition that per protocol or in the opinion of the investigator is incompatible with the study.\n- Patients with known allergy or severe hypersensitivity to any of the trial drugs or their excipients\n- Other concurrent medical or psychiatric condition that, in the Investigator's opinion, may cause misleading study interpretation or prevent completion of study procedures and followup examinations.\n- Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment are not eligible.\n- Patients enrolled in another therapeutic trial within 30 days of inclusion\n- 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\n- Person deprived of their liberty or under protective custody or guardianship\n- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons."}

Primary endpoints

• {"endpoint_text":"- Overall survival estimated by the Kaplan-Meier method will be used as primary efficacy outcome. Overall survival is defined as the interval between the date of randomization and the date of death from any cause. Alive patients will be censored at the date of last follow-up.","definition_or_measurement_approach":"Overall survival estimated by the Kaplan-Meier method; defined as interval between date of randomization and date of death from any cause; alive patients censored at date of last follow-up."}

Secondary endpoints

• {"endpoint_text":"- Efficacy : The clinical benefit rate (CBR), defined as the percentage of patients with a complete response (CR, defined as a disappearance of all target lesions), a partial response (PR, defined as at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease for at least 24 weeks","definition_or_measurement_approach":"CBR defined as percentage of patients with CR, PR, or SD lasting at least 24 weeks; response assessments per criteria described (CR disappearance of all target lesions; PR ≥30% decrease in sum diameters)."}
• {"endpoint_text":"- Efficacy : Objective response rate (ORR), defined as the percentage of patients with a complete response (CR, defined as a disappearance of all target lesions) or a partial response (PR, defined as at least a 30% decrease in the sum of diameters of target lesions).","definition_or_measurement_approach":"ORR defined as percentage of patients with CR or PR (CR disappearance of all target lesions; PR ≥30% decrease in sum diameters)."}
• {"endpoint_text":"- Efficacy : The progression-free survival (PFS), defined as the interval between the date of randomization and the date of progression or death from any cause, whichever occurs first. A patient alive and without progression will be censored at the date of last follow-up.","definition_or_measurement_approach":"PFS defined as interval between randomization and progression or death; patients alive without progression censored at last follow-up."}
• {"endpoint_text":"- Efficacy : Quality adjusted PFS (QA-PFS) calculated as the product of the PFS function and the overall health utility index EQ-5D-5L.","definition_or_measurement_approach":"QA-PFS calculated as product of PFS function and overall health utility index EQ-5D-5L."}
• {"endpoint_text":"- Safety and Quality of life : Safety and tolerability of sacituzumab govitecan will be evaluated by the frequency and severity of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs) graded according to the NCI-CTCAE v5.0; The proportion of treatment discontinuations, interruptions and dose reductions due to any AEs will also be measured.","definition_or_measurement_approach":"Safety assessed by frequency/severity of AEs, SAEs, AESIs graded per NCI-CTCAE v5.0; proportions of treatment discontinuations, interruptions and dose reductions due to AEs measured."}
• {"endpoint_text":"- Safety and Quality of life : Mean changes from Baseline in Global Health Status/Quality of Life (GHS/QoL) will be measured at week 24 via the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30).","definition_or_measurement_approach":"Mean changes from baseline in GHS/QoL measured at week 24 using EORTC QLQ-C30."}

France

Earliest CTIS Part Ii Submission Date

22-07-2025

Latest Decision Or Authorization Date

23-10-2025

Processing Time Days

93

Number Of Sites

19

Number Of Participants

260

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France