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Trial record 1 of 1 for:    ZW25-201
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A Safety and Efficacy Study of ZW25 Plus Combination Chemotherapy in HER2-expressing Gastroesophageal Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT03929666
Recruitment Status : Recruiting
First Posted : April 29, 2019
Last Update Posted : April 29, 2019
Sponsor:
Information provided by (Responsible Party):
Zymeworks Inc.

Tracking Information
First Submitted Date  ICMJE February 22, 2019
First Posted Date  ICMJE April 29, 2019
Last Update Posted Date April 29, 2019
Actual Study Start Date  ICMJE April 10, 2019
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • Incidence of dose-limiting toxicities (DLTs) (Part 1) [ Time Frame: Up to 6 weeks ]
    Number of participants who experienced a DLT. DLTs include adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen.
  • Incidence of adverse events (Part 1) [ Time Frame: Up to 11 months ]
    Number of participants who experienced an adverse event
  • Incidence of lab abnormalities (Part 1) [ Time Frame: Up to 11 months ]
    Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
  • Objective response rate (ORR) (Part 2) [ Time Frame: Up to 10 months ]
    Number of participants who achieved a best response of either complete or partial response during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • Objective response rate (ORR) (Part 1) [ Time Frame: Up to 10 months ]
    Number of participants who achieved a best response of either complete or partial response during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Disease control rate (Parts 1 and 2) [ Time Frame: Up to 10 months ]
    Number of participants who achieved a best response of complete response, partial response, or stable disease during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Duration of response (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median duration of response (in months) and range (minimum, maximum)
  • Progression-free survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median progression-free survival (in months) and range (minimum, maximum)
  • Overall survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median overall survival (in months) and range (minimum, maximum)
  • Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) [ Time Frame: Up to 11 months ]
    Number of participants who develop ADAs
  • End of infusion concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • Maximum serum concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • Trough concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • Incidence of adverse events (Part 2) [ Time Frame: Up to 11 months ]
    Number of participants who experienced an adverse event
  • Incidence of lab abnormalities (Part 2) [ Time Frame: Up to 11 months ]
    Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of ZW25 Plus Combination Chemotherapy in HER2-expressing Gastroesophageal Adenocarcinoma
Official Title  ICMJE Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastroesophageal Adenocarcinoma (GEA)
Brief Summary This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor activity of ZW25 plus physician's choice of combination chemotherapy in HER2-expressing gastroesophageal adenocarcinoma (GEA). Eligible patients include those with unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA.
Detailed Description Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus physician's choice of first-line combination chemotherapy (XP, FP, or mFOLFOX6) and will confirm the recommended dosage (RD) of ZW25 when administered in combination with each of these multi-agent chemotherapy regimens. Then, Part 2 of the study will evaluate the anti-tumor activity of ZW25 plus physician's choice of combination chemotherapy in HER2-high GEA.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-expressing Gastroesophageal Adenocarcinoma
Intervention  ICMJE
  • Drug: ZW25
    • Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
    • Part 2: RD identified in Part 1
  • Drug: Capecitabine
    Administered orally twice daily (PO bid)
  • Drug: Cisplatin
    Administered IV
  • Drug: Fluorouracil
    Administered IV
  • Drug: Leucovorin
    Administered IV
  • Drug: Oxaliplatin
    Administered IV
Study Arms  ICMJE
  • Experimental: ZW25 + XP
    ZW25 plus capecitabine and cisplatin
    Interventions:
    • Drug: ZW25
    • Drug: Capecitabine
    • Drug: Cisplatin
  • Experimental: ZW25 + FP
    ZW25 plus fluorouracil (5-FU), leucovorin, and cisplatin
    Interventions:
    • Drug: ZW25
    • Drug: Cisplatin
    • Drug: Fluorouracil
    • Drug: Leucovorin
  • Experimental: ZW25 + mFOLFOX6
    ZW25 plus 5-FU, leucovorin, and oxaliplatin
    Interventions:
    • Drug: ZW25
    • Drug: Fluorouracil
    • Drug: Leucovorin
    • Drug: Oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2019)
91
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2023
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

  • Disease diagnosis:

    • Part 1: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+ or 2+ with or without gene amplification based upon local assessment)
    • Part 2: Unresectable, locally advanced, recurrent or metastatic HER2-high GEA (IHC 3+, or IHC 2+ and FISH+ by central review)
  • Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1:

    • Part 1: Measurable or non-measurable disease
    • Part 2: Measurable disease
  • ECOG performance status score of 0 or 1
  • Adequate organ function
  • Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal

Exclusion:

  • Prior treatment with a HER2-targeted agent
  • Treatment with prior anti-cancer therapy, except prior adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to study treatment dosing
  • Untreated known brain metastases (patients with treated brain metastases who are off steroids and are stable for at least 1 month at the time of screening are eligible)
  • Having clinically significant cardiac disease or known myocardial infarction or unstable angina (within 6 months before first study treatment dosing)
  • QTc Fridericia (QTcF) > 450 ms
  • Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0
  • Clinically significant interstitial lung disease
  • Known active hepatitis B or C (per the Centers for Disease Control guidelines) or known infection with human immunodeficiency virus (HIV)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03929666
Other Study ID Numbers  ICMJE ZWI-ZW25-201
Has Data Monitoring Committee No
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party Zymeworks Inc.
Study Sponsor  ICMJE Zymeworks Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Rose Lai, MD, MS Zymeworks Inc.
PRS Account Zymeworks Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP