Trastuzumab deruxtecan for Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- 1.\tWomen (or men) aged ≥ 18 years on the day of signing the informed consent with histologically proven breast cancer.\n- 10.\tPatient affiliated to a Social Health Insurance in France.\n- 2.\tMetastatic or locally advanced breast cancer with overerexpression/amplification HER2 (IHC +++ or ++ and positive-hybridation in situ) or low HER2 expression (IHC + or ++ and negative-hybridation in situ) and may be ultra-low (in first line, in case of approval).\n- 3.\tPatient eligible for Trastuzumab-Deruxtecan (T-DXd).\n- 4.\tConcomitant administration of pertuzumab may be accepted in case of approval in first line for HER2-overexpressed/amplified locally advanced or metastatic breast cancer.\n- 5.\tFemale subjects of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study treatment.\n- 6.\tFemale subjects of childbearing potential must be willing to follow at least one method of contraception or be surgically sterile, or abstain from heterosexual activity for the duration of the study and until 7 months after the last dose of study treatment. Subjects of childbearing potential are those who have not been surgically sterilized and who had menstruation in the last 12 months. Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.\n- 7.\tMale subjects must agree to use at least one method of contraception for the duration of the study and until 4 months after the last dose of study treatment. Note: Abstinence is acceptable if it is the subject's usual lifestyle and preferred method of contraception.\n- 8.\tSigned written informed consent.\n- 9.\tPatient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol."}

Exclusion criteria

• {"criterion_text":"- 1.\tPeripheral venous access making blood samples difficult.\n- 10.\tPatient with severe hepatic impairment defined by TGO and/or TGP > 5 x ULN and Total bilirubin > 1.5 x ULN.\n- 2.\tPatient unable to receive T-DXd treatment at a dose of 5.4 mg/kg in cycle 1 (whatever the reason).\n- 3.\tPatient with known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.\n- 4.\tPatient with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.\n- 5.\tPatient pregnant, or breast-feeding.\n- 6.\tAny psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure.\n- 7.\tPatient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).\n- 8.\tConcurrent participation in an experimental drug study.\n- 9.\tPatient with a known history of hypersensitivity to the active substance of T-DXd or to any of the excipients listed in the SmPC of T-DXd."}

Primary endpoints

• {"endpoint_text":"- Plasma exposure of free-DXd (payload) will be measured by the cumulative AUC (Area under the concentration vs. time curve) over the first 3 cycles or until an event (interruption or dose concession for toxicity) divided by the number of corresponding cycles. These AUCs will be determined by Bayesian estimation (Posthoc values) using a non-linear mixed-effects approach. Differences between the two groups will be assessed using Student’s test (or Mann Whitney if applicable).","definition_or_measurement_approach":"Measured by the cumulative AUC over the first 3 cycles or until an event, divided by number of corresponding cycles; AUCs determined by Bayesian estimation (Posthoc) using a non-linear mixed-effects approach; group differences assessed with Student's t-test (or Mann-Whitney if applicable)."}

Secondary endpoints

• {"endpoint_text":"- \t Safety: Safety will be assessed through recording of adverse events using NCI-CTCAE toxicity classification v5.0. AEs will be summarized by descriptive statistics and differences between groups will be assessed using Chi-squared or Fisher’s exact test.","definition_or_measurement_approach":"Safety via recording of adverse events using NCI-CTCAE v5.0; AEs summarized descriptively; group differences assessed using Chi-squared or Fisher's exact test."}
• {"endpoint_text":"- \tEfficacy: The Kaplan-Meier approach will be used to estimate PFS rates for each group. To consider immortal time bias, the association between plasma exposure (or plasma concentration) and PFS will be assessed using a Cox proportional hazards model with time-dependent variable. Cox model will be adjusted on clinico-pathological variables of interest. A complementary analysis will be conducted using Landmark approach at different time points.","definition_or_measurement_approach":"PFS estimated by Kaplan-Meier; association between plasma exposure and PFS assessed using Cox proportional hazards model with time-dependent variable adjusted for clinico-pathological covariates; complementary Landmark analyses planned."}
• {"endpoint_text":"- \tAssociation between Progression Free Survival and body composition will be assessed using a similar approach to the one used for association with plasma exposure.","definition_or_measurement_approach":"Association assessed using similar methods as plasma exposure analyses (time-dependent Cox models / adjusted analyses / Landmark approaches)."}
• {"endpoint_text":"- \tAssociation between plasma exposure and safety will be assessed using logistic regression models. The ORs and corresponding confidence intervals (CIs) will be reported.","definition_or_measurement_approach":"Association between plasma exposure and safety (AEs) assessed using logistic regression models with reporting of odds ratios and confidence intervals."}

France

Earliest CTIS Part Ii Submission Date

04-09-2025

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

195

Number Of Sites

11

Number Of Participants

210

Primary sponsor

Full Name

Oncopole Claudius Regaud

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Ligue nationale Contre le Cancer","duties_or_roles":"Source of monetary support","organisation_type":""}