A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer
- Registration Number
- NCT04739761
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is open-label, multicenter, international study, assessing the efficacy and safety of Trastuzumab deruxtecan (T-DXd) in participants with or without brain metastasis (BMs), with previously-treated advanced/metastatic HER2-positive breast cancer whose disease has progressed on prior anti-HER2-based regimens and who received no more than 2 lines/regimens of therapy in the metastatic setting (excluding tucatinib).
- Detailed Description
Approximately 500 eligible participants will be enrolled into 1 of 2 cohorts (250 participants in each cohort) according to the presence or absence of BMs at baseline. Cohort 1 will include participants without BM at baseline and Cohort 2 will consist of participants with BM at baseline.
After study intervention discontinuation, all participants will undergo an end-of-treatment visit (within 7 days of discontinuation) and will be followed up for safety assessments 40 (+ up to 7) days after the discontinuation of all study intervention.
All participants will be followed up for survival status and duration of treatment on subsequent therapies after intervention discontinuation every 3 months (± 14 days) from the date of the safety follow-up until death, withdrawal of consent, or the end of the study, as per defined in the protocol.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 506
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Trastuzumab Deruxtecan Trastuzumab Deruxtecan Participants with or without BM at baseline will receive intravenous (IV) T-DXd, 5.4 mg/kg, every 3 weeks (21-day cycle) until Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) defined radiological progression outside central nervous system, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) in Participants with BM at Baseline (Cohort 2) From screening until PD (Up to 2.5 Years) To describe the overall treatment effect of T- DXd in HER2-positive MBC participants with baseline BM. The PFS will be defined as the time from the date of the first dose of study intervention until the date of objective PD per RECIST 1.1 as assessed by ICR or death.
Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1) From screening until progression of disease [PD] (Up to 2.5 Years) To describe the overall treatment effect of T- DXd in HER2-positive metastatic breast cancer (MBC) participants without baseline BM. An ORR is defined as the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by independent central review (ICR) per RECIST 1.1.
- Secondary Outcome Measures
Name Time Method Time to Progression Screening Day (-28 days) until PD (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. Time to progression by RECIST 1.1 per ICR is defined as the time from the date of the first dose of study intervention to the date of documented disease progression.
Site (CNS vs extracranial vs both) of Next Progression Screening Day (-28 days) until next PD (Approximately 2.5 Years) To describe the treatment effect on the development and progression (CNS progression) of BM in participants without baseline BM using additional efficacy measurements. Site of next progression will be summarized descriptively in participants who develop isolated CNS progression, receive local therapy, continue on protocol therapy, and have a subsequent documented disease progression (CNS or extracranial) per RECIST 1.1.
Central Nervous System Objective Response Rate in Participants with BM at Baseline by ICR (Cohort 2) Screening Day (-28 days) until EOT (Approximately 2.5 Years) To describe efficacy in participants with stable or untreated BM. The CNS ORR is defined as the proportion of participants with measurable BM at baseline who have a confirmed CR or confirmed PR of brain lesions, as determined by ICR per CNS RECIST 1.1.
Number of Participants with Investigator-assessed ILD/Pneumonitis or Rate of Investigator-assessed ILD/Pneumonitis Cycle 1 (15 days ± 2 days) Day 1 until C4 (15 days ± 2 days) Day 1 and thereafter subsequent cycles until PD (Approximately 2.5 Years) To describe the safety profile of T-DXd.
Duration of Treatment on Subsequent Lines of Therapy At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. Duration of treatment on subsequent therapy will be defined as the time from the date of first dose of a subsequent therapy until date of the last dose of that therapy.
MD Anderson Symptom Inventory Brain Tumor-specific Items Cycle 1 (15 days ± 2 days) Day 1, thereafter q3w until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years) To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM.
Number of Participants with Adverse Events Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years) To describe the safety profile of T-DXd.
Number of Participants with Adverse Events with BM at Baseline Cycle 1 (15 days ± 2 days) Day 1 until safety F/U (40+7 days after last dose) (Approximately 2.5 Years) To describe the safety profile of T-DXd.
Overall Survival (OS) in Months At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. An OS is defined as the time from the date of the first dose of study intervention until death due to any cause.
Duration of Response (DoR) Screening Day (-28 days) until end-of-treatment (EOT) (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. The DoR will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by ICR or death due to any cause.
Central Nervous System Progression-free Survival in Participants with BM at Baseline (Cohort 2) At safety follow-up (40+7 days after last dose) then survival F/U q3months ± 14 days (Approximately 2.5 Years) To describe efficacy in participants with stable or untreated BM. The CNS PFS is defined as time from the first dose of study intervention to CNS progression per CNS RECIST 1.1 or death resulting from any cause, whichever occurs first.
Time to Second Progression or Death (PFS2) At safety F/U (40+7 days after last dose) visit, thereafter survival F/U q3months ± 14 days (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants with or without baseline BM using additional efficacy measurements. The PFS2 is defined as time from the first dose of study intervention to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death.
Incidence of new Symptomatic Central Nervous System (CNS) Metastasis During Treatment in Participants without BM at Baseline (Cohort 1) At Screening day (-28 days), Cycle 1 (15 days ± 2 days) Day 1 and Cycle 3 (15 days ± 2 days) Day 1 and thereafter every 3 subsequent cycles (Approximately 2.5 Years) To describe the treatment effect on the development and progression of BM in participants without baseline BM using additional efficacy measurements.
Time to Next Progression (CNS or extracranial) or Death Screening Day (-28 days) until next PD (Approximately 2.5 Years) To describe the treatment effect on the development and progression (central nervous system \[CNS\] progression) of BM in participants without baseline BM using additional efficacy measurements. The time to next progression is defined as the time from the date of the first documented isolated CNS progression to the date of the next documented disease progression (CNS or extracranial) per RECIST 1.1 or death, and will be summarized descriptively in participants who develop isolated CNS progression, receive local therapy, and continue on protocol therapy.
Objective Response Rate in Participants with BM at Baseline (Cohort 2) From screening until PD (Up to 2.5 Years) To describe efficacy in participants with stable or untreated BM. An ORR will be evaluated by RECIST 1.1 per ICR.
Neurologic Assessment in Neuro-Oncology Scale Cycle 1 (15 days ± 2 days [Day 1]), Cycle 2 (15 days ± 2 days) Day 1, Cycle 3 (15 days ± 2 days) Day 1, Cycle 4 (15 days ± 2 days) Day 1 thereafter subsequent Cycles until PD and at EOT visit (Approximately 2.5 Years) To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM.
Time to new CNS Lesions in Participants with BM at Baseline (Cohort 2) Screening Day (-28 days) until EOT (Approximately 2.5 Years) To describe efficacy in participants with stable or untreated BM. The time to new CNS lesions is defined as the time from the date of the first dose of study intervention to the date of documented new CNS lesions.
Central Nervous System Duration of Response in Participants with BM at Baseline (Cohort 2) Screening Day (-28 days) until EOT (Approximately 2.5 Years) To describe efficacy in participants with stable or untreated BM. The CNS DoR will be defined as the time from the date of first documented confirmed CNS response until date of documented CNS progression per CNS RECIST 1.1 as assessed by ICR or death due to any cause.
Cognitive Functions Tests Cycle 1 (15 days ± 2 days) Day 1, thereafter q12w and at EOT visit (Approximately 2.5 Years) To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM.
St. George's Respiratory Questionnaire - idiopathic pulmonary fibrosis version in Participants with Interstitial Lung Disease (ILD)/Pneumonitis After diagnosis of ILD/pneumonitis and thereafter once weekly until EOT and safety F/U (40+7 days after last dose) (Approximately 2.5 Years) To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline BM.
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Cycle 1 (15 days ± 2 days) Day 1, thereafter every 3 weeks (q3w) until 24 weeks post EOT visit and prior to second progression, and at the EOT visit (Approximately 2.5 Years) To describe the effect of T-DXd on symptoms, functioning, and health-related quality of life (HRQoL) in HER2+ MBC participants with or without baseline BM.
Trial Locations
- Locations (1)
Research Site
🇬🇧Edinburgh, United Kingdom