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

• ClinicalTrials.gov Identifier: NCT03262935
• Recruitment Status: Completed
• First Posted: August 25, 2017
• Results First Posted: October 19, 2023
• Last Update Posted: October 19, 2023
• Sponsor: Byondis B.V.
• Information provided by (Responsible Party): Byondis B.V.

Tracking Information

• First Submitted Date: August 16, 2017
• First Posted Date: August 25, 2017
• Results First Submitted Date: June 30, 2023
• Results First Posted Date: October 19, 2023
• Last Update Posted Date: October 19, 2023
• Actual Study Start Date: December 15, 2017
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2023)

Progression Free Survival [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 23, 2017)

Progression Free Survival [ Time Frame: Up to 2 years from baseline ]

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.

Current Secondary Outcome Measures (submitted: August 18, 2023)

• Overall Survival [ Time Frame: 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 [ Time Frame: 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.
• Investigator Assessed Progression Free Survival [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: August 23, 2017)

• Overall Survival [ Time Frame: 2-year overall survival ]
  Overall survival is defined as the time from date of randomization to death due to any cause.
• Objective Response Rate [ Time Frame: Up to 2 years from baseline ]
  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.
• Investigator assessed Progression Free Survival [ Time Frame: Up to 2 years from baseline ]
  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 [ Time Frame: Up to 2 years ]
  Standard EORTC questionnaire

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
• Official Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• Drug: (vic-)trastuzumab duocarmazine
  Intravenous SYD985, Q3W
  Other Names:

  • SYD985
  • Trastuzumab vc-seco-DUBA
• Drug: Physician's choice
  See drug label
  Other Names:

  • Lapatinib (Lap)
  • Capecitabine (Cap)
  • Trastuzumab (T)
  • Vinorelbine (Vino)
  • Eribulin (Eri)

Study Arms

• Experimental: (vic-)trastuzumab duocarmazine
  SYD985, every 3 weeks (Q3W)
  Intervention: Drug: (vic-)trastuzumab duocarmazine
• Active Comparator: Physician's choice
  1. Lap/Cap
  2. T/Cap
  3. T/Vino
  4. T/Eri
  Intervention: Drug: Physician's choice

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2023): 437
• Original Estimated Enrollment (submitted: August 23, 2017): 345
• Actual Study Completion Date: June 30, 2022
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Denmark, France, Italy, Netherlands, Singapore, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03262935
• Other Study ID Numbers: SYD985.002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Byondis B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Byondis B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Evelyn van den Tweel, PhD; Byondis B.V., The Netherlands

• PRS Account: Byondis B.V.
• Verification Date: June 2023