A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT05104866
- Lead Sponsor
- AstraZeneca
- Brief Summary
The study will evaluate the safety and efficacy of datopotamab deruxtecan (also known as Dato-DXd, DS-1062a), when compared with Investigator's choice of standard of care single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in participants with inoperable or metastatic HR-positive, HER2- negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.
- Detailed Description
The primary objective of this study will assess the safety and efficacy of datopotamab deruxtecan (Dato-DXd) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.
The study will be stratified based on number of previous lines of chemotherapy (1 vs. 2), prior use of CDK4/6 inhibitors (Yes vs. no) and geographic region of participant (US/Canada/Europe vs. rest of world).
This study aims to see if datopotamab deruxtecan allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 732
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigators Choice of Chemotherapy (ICC) Capecitabine Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine Investigators Choice of Chemotherapy (ICC) Gemcitabine Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine Investigators Choice of Chemotherapy (ICC) Eribulin Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine Investigators Choice of Chemotherapy (ICC) Vinorelbine Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine Dato-DXd Dato-DXd Arm 1: Dato-DXd
- Primary Outcome Measures
Name Time Method Progression Free Survival From randomization until progression as assessed by BICR or death due to any cause (anticipated to be 21 months after the first participant has been randomized) PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1. The measure of interest is the hazard ratio of PFS.
Overall Survival Approximately 44 months after the first participant has been randomized OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS.
- Secondary Outcome Measures
Name Time Method Time from randomization to second progression or death (PFS2) From randomization to second progression or death (anticipated to be up to 21 months) Time to second progression of death will be defined as the time from the randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.
Clinical Outcome Assessment- TTD in pain From randomization to 18 weeks post-progression The secondary PRO endpoints include: TTD in pain as measured by the pain scale from EORTC QLQ-C30
Pharmacokinetics of Dato-DXd From first dose to end of treatment (anticipated to be up to 21 months). Plasma concentrations of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload).
Immunogenicity From first dose to end of treatment safety follow-up (anticipated to be up to 22 months). To test for the presence of ADA to investigate the immunogenicity of Dato-DXd.
Objective Response Rate (ORR) Randomization to event (response, progression, last evaluable assessment) anticipated to be up to 21 months Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1.
Duration of Response (DoR) From randomization to event up to 21 months; from date of first response until progression or death up to 20 months Duration of response is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/Investigator assessment or death due to any cause.
Progression-Free Survival by Investigator assessment From randomization to progression (investigator assessment) or death (anticipated to be up to 21 months) PFS by Investigator assessment will be defined as the time from the date of randomization until the date of PD per RECIST 1.1 (by Investigator assessment) or death (by any cause in the absence of progression), (ie, date of event or censoring - date of randomization + 1).
Clinical Outcome Assessment- TTD in GHS From randomization to 18 weeks post-progression The secondary PRO endpoints include: TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC QLQ-C30
Disease Control Rate (DCR) At least 11 weeks after randomization up to 18 months. Disease control rate at 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD, per RECIST 1.1, as assessed BICR/per investigator assessment and derived from the raw tumor data for at least 11 weeks after randomization.
Time to First Subsequent Therapy (TFST) From randomization to start of first subsequent anti-cancer therapy post discontinuation of randomized treatment (anticipated to be up to 21 months) Time to first subsequent therapy is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.
Time to Second Subsequent Therapy (TSST) From randomization to start of second subsequent anti-cancer therapy post discontinuation of first subsequent therapy (anticipated to be up to 21 months) Time to second subsequent therapy is defined as the time from randomization to until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.
Clinical Outcome Assessment- TTD in physical Functioning From randomization to 18 weeks post-progression The secondary PRO endpoints include: TTD in physical functioning as measured by the physical functioning scale from EORTC QLQ-C30
Trial Locations
- Locations (1)
Research Site
🇬🇧Truro, United Kingdom