TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd
NCT Number: NCT06533826
Acronym: TRADE DXd
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Breast Cancer|HER2-low Breast Cancer|Metastatic Breast Cancer
Interventions: DRUG: Trastuzumab Deruxtecan|DRUG: Datopotamab Deruxtecan
Sponsor: Ana C Garrido-Castro, MD
Collaborators: AstraZeneca|Translational Breast Cancer Research Consortium
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 357
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2025-01
Completion Date: 2038-08-01
Locations: Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States

Summary:
The purpose of this study is to test the safety and effectiveness of the sequence of two investigational drugs (trastuzumab deruxtecan followed by datopotamab deruxtecan, or datopotamab deruxtecan followed by trastuzumab deruxtecan) to learn whether the treatment works in treating HER2-low metastatic breast cancer.

The names of the study drugs involved in this study are:

* Datopotamab deruxtecan (a type of antibody drug conjugate)
* Trastuzumab deruxtecan (a type of antibody drug conjugate)

Primary Outcome Measures: Objective Response Rate in ADC1 (Group 1) Cohort, Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol., The observation period related to this endpoint is up to 36 months.|Objective Response Rate in ADC2 (Group 2) Cohort, Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using RECIST 1.1 criteria as defined per protocol., The observation period related to this endpoint is up to 36 months.
Secondary Outcome Measures: Median Progression Free Survival in ADC1 (Group 1) Cohort, PFS based on Kaplan-Meier methodology will be defined as the time from randomization until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation., The observation period related to this endpoint is up to 36 months.|Median Overall Survival (OS) in ADC1 (Group 1) Cohort, Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant., The observation period related to this endpoint is up to 5 years.|Clinical Benefit Rate (CBR) in ADC1 (Group 1) Cohort, Clinical Benefit Rate (CBR) is defined as the proportion of participants with CR, PR and stable disease (SD) for ≥ 24 weeks as the best overall response., The observation period related to this endpoint is up to 36 months.|Time to Progression (TTP) in ADC1 (Group 1) Cohort, Time to Progression (TTP) is defined as the time from registration to ADC1 to progression, or censored at date of last disease evaluation for those without progression reported based on Kaplan-Meier methodology., The observation period related to this endpoint is up to 36 months.|Time to Response (TTR) in ADC1 (Group 1) Cohort, The time to objective response is defined as the time from registration to the date of the first documented CR or PR (whichever is first recorded)., The observation period related to this endpoint is up to 36 months.|Duration of Response (DOR), The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause). Participants without reported events are censored at the last disease evaluation., The observation period related to this endpoint is up to 36 months.|Grade 3-5 Treatment-Related Toxicity Rate in ADC1 (Group 1) Cohort, The percentage of participants who experienced a maximum grade 3-5 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms., The observation period related to this endpoint is up to 36 months.|Change in HER2 Expression from Baseline to Progression, The evaluation of change in HER2 expression within each cohort will be based on a paired t-test (absolute difference) using a two-sided alpha = 0.05 for each cohort with no adjustment for multiplicity due to the exploratory nature of these analyses., The observation period related to this endpoint is up to 36 months.|Change in TROP2 Expression from Baseline to Progression, The evaluation of change in TROP2 expression within each cohort will be based on a paired t-test (absolute difference) using a two-sided alpha = 0.05 for each cohort with no adjustment for multiplicity due to the exploratory nature of these analyses., The observation period related to this endpoint is up to 36 months.|Median Progression Free Survival in ADC2 (Group 2) Cohort, PFS based on Kaplan-Meier will be defined as the time from registration (external ADC2 patients) or entry into ADC2 (confirmation of eligibility for ADC2 for cross-over patients from ADC1) until the identification of disease progression or death, whichever occurs first. Subjects without disease progression or death at the time of analysis will be censored at the date of last disease evaluation., The observation period related to this endpoint is up to 36 months.|Median Overall Survival (OS) in ADC2 (Group 2) Cohort, Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant., The observation period related to this endpoint is up to 5 years.|Clinical Benefit Rate (CBR) in ADC2 (Group 2) Cohort, Clinical Benefit Rate (CBR) is defined as the proportion of participants with CR, PR and stable disease (SD) for ≥ 24 weeks as the best overall response., The observation period related to this endpoint is up to 36 months.|Time to Progression (TTP) in ADC2 (Group 2) Cohort, Time to Progression (TTP) is defined as the time from registration to ADC2 to progression, or censored at date of last disease evaluation for those without progression reported based on Kaplan-Meier methodology., The observation period related to this endpoint is up to 36 months.|Time to Response (TTR) in ADC2 (Group 2) Cohort, The time to objective response is defined as the time from registration to the date of the first documented CR or PR (whichever is first recorded)., The observation period related to this endpoint is up to 36 months.|Duration of Response (DOR) in ADC2 (Group 2) Cohort, The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause). Participants without events reported are censored at the last disease evaluation., The observation period related to this endpoint is up to 36 months.|Grade 3-5 Treatment-Related Toxicity Rate in ADC2 (Group 2) Cohort, The percentage of participants who experienced a maximum grade 3-5 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms., The observation period related to this endpoint is up to 36 months.|Health-Related Quality of Life (HRQoL) from Baseline to Progression in ADC1 (Group 1) Cohort, The evaluation of change in HRQoL will be summarized based on EORTC QLQ-C30 scores for the derived functional and symptom quality of life scales according to the scoring manuals. All the derived scales range in score from 0 to 100. For the overall HRQOL and functioning scales, a higher score is correlated with better HRQOL, whereas a higher score represents worse HRQOL for symptom scales. Global health status scores will be reported independently for patients who receive T-DXd as ADC1 and for those who receive Dato-DXd as ADC1., The observation period related to this endpoint is up to 36 months.