SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that SYD985 [(vic-)trastuzumab duocarmazine] is superior to physician's choice in prolonging progression free survival.

Detailed Description
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This study is designed as a randomized, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. The patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment. Eligible patients will be randomly assigned (2:1) to receive SYD985 or physician's choice treatment until disease progression, unacceptable toxicity or study termination by the Sponsor. During treatment, patients will have to visit the clinical site to assess efficacy, quality of life (QoL), and safety using standardized criteria.

Official Title
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A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: (vic-)trastuzumab duocarmazine
* Drug: Physician's choice


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer; Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease; HER2-positive tumor status; Patients must have measurable or non-measurable disease that is evaluable per RECIST 1.1; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; Estimated life expectancy > 12 weeks at randomization; Adequate organ function and blood cell counts. Main Exclusion Criteria: Current or previous use of a prohibited medication as listed in the protocol; History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine; History of keratitis; Severe, uncontrolled systemic disease at screening; Left Ventricular Ejection Fraction (LVEF) < 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine; Cardiac troponin value above the Upper Limit of Normal (ULN); History of clinically significant cardiovascular disease; Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization; History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (vic-)trastuzumab duocarmazine<br>SYD985, every 3 weeks (Q3W) | Drug: (vic-)trastuzumab duocarmazine<br>* Intravenous SYD985, Q3W<br>* Other names: Trastuzumab vc-seco-DUBA;|
| Active Comparator: Physician's choice<br>Lap/Cap T/Cap T/Vino T/Eri | Drug: Physician's choice<br>* See drug label<br>* Other names: Eribulin (Eri);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by central assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred earlier. | baseline until primary analysis data cut-off date of 31March2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from date of randomization to death due to any cause. | baseline until final Overall Survival analysis data cut-off date of 30June2022 | 
| Objective Response Rate | Objective Response Rate is defined as the proportion of patients with a centrally assessed best overall response of complete response or partial response according to RECIST v1.1. | baseline until primary analysis data cut-off date of 31March2021 | 
| Investigator Assessed Progression Free Survival | Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier. | baseline until primary analysis data cut-off date of 31March2021 | 
| Patient Reported Outcomes for Health Related Quality of Life | Change in the global health status/Quality of Life (QoL) scale score of the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 from baseline (cycle 1). The raw score (1 to 7) has been transformed to a score ranging from 0 to 100. A higher score means a better outcome: hence a positive change from baseline means an improvement in global health status/Quality of Life and a negative change from baseline means a worsening of global health status/Quality of Life. | baseline until primary analysis data cut-off date of 31March2021 |