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

Phase 3

Completed

Interventions: Drug: (vic-)trastuzumab duocarmazine
Drug: Physician's choice

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
(vic-)trastuzumab duocarmazine	(vic-)trastuzumab duocarmazine	SYD985, every 3 weeks (Q3W)
Physician's choice	Physician's choice	1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	baseline until primary analysis data cut-off date of 31March2021	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.

Secondary Outcome Measures

Name	Time	Method
Investigator Assessed Progression Free Survival	baseline until primary analysis data cut-off date of 31March2021	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.
Patient Reported Outcomes for Health Related Quality of Life	baseline until primary analysis data cut-off date of 31March2021	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.
Overall Survival	baseline until final Overall Survival analysis data cut-off date of 30June2022	Overall survival is defined as the time from date of randomization to death due to any cause.
Objective Response Rate	baseline until primary analysis data cut-off date of 31March2021	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.

Locations (89): Southern Cancer Center
🇺🇸
Mobile, Alabama, United States
Arizona Clinical Research Center
🇺🇸
Tucson, Arizona, United States
Moores UCSD Cancer Center
🇺🇸
San Diego, California, United States
Woodlands Medical Specialists
🇺🇸
Pensacola, Florida, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Cancer Center of Kansas
🇺🇸
Wichita, Kansas, United States
University of Maryland Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
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Southern Cancer Center
🇺🇸Mobile, Alabama, United States