Studieoverzicht - 2021-04 TROPION-Breast01
| Principal Investigator(s) | ||||
| Study manager | Bas Zuidema, local study manager AstraZeneca |
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| Central datamanagement and randomization | AstraZeneca | |||
| Monitoring | AstraZeneca | |||
| Local datamanagement | AstraZeneca | |||
| Funding | AstraZeneca | |||
| Extra | Deelnemende centra: Ikazia VieCuri Amsterdam UMC, locatie VUmc | |||
A Phase 3, Randomized, Multi-center, Open-label Study
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.
- Progression Free Survival [ Time Frame: From randomization until progression as assessed by BICR or death due to any cause (anticipated to be 21 months) ]
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 [ Time Frame: Approximately 44 months ]
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.
- Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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).
- Disease Control Rate (DCR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
- Time from randomization to second progression or death (PFS2) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
- Clinical Outcome Assessment- TTD in physical Functioning [ Time Frame: 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
- Clinical Outcome Assessment- TTD in GHS [ Time Frame: 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
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Participant must be ≥ 18 years (≥ 20 years in Japan) at the time of screening.
- Inoperable or metastatic HR-positive, HER2-negative breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive [ER or PgR ≥ 1%]) and HER2-negative. If a participant had multiple results after metastatic disease, the most recent local test result will be used to confirm eligibility.
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Progressed on or not suitable for endocrine therapy per investigator assessment, and treated with 1 to 2 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy.
Note: If a chemotherapy drug is changed within 28 days of use to another drug in the same class (ie, antimetabolite to antimetabolite) for any reason, the first drug is not counted as a line. Targeted agents (such as mTOR inhibitors, PD-1/PD-L1 inhibitors, PARP inhibitors), endocrine therapies, and CDK4/6 inhibitors on their own do not contribute to the count of prior lines of chemotherapy; however, regimens with such agents in combination with metastatic chemotherapy should be classified as one line of chemotherapy.
- Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment. Note: Participants who previously received any of these agents are eligible for enrolment to another ICC agent in this study.
- ECOG PS of 0 or 1, with no deterioration over the previous 2 weeks prior to day of first dosing.
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At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1. Target Lesion at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI, which is suitable for accurate repeated measurements.
Note: Participants with bone-only metastases are not permitted.
- Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants, may be included in the study, if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment.
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Adequate organ and bone marrow function within 7 days before day of first dosing.
- LVEF ≥ 50% by either an echocardiogram or MUGA within 28 days of first dosing.
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Minimum life expectancy of 12 weeks at screening.
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Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies; however, oral estrogens are not permitted.
Deelnemende centra:
Ikazia
VieCuri
Amsterdam UMC, locatie VUmc
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