Clinical Trials /

A Safety and Efficacy Study of ZW25 Plus Combination Chemotherapy in HER2-expressing Gastroesophageal Adenocarcinoma

NCT03929666

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Efficacy Study of ZW25 Plus Combination Chemotherapy in HER2-expressing Gastroesophageal Adenocarcinoma
  • Official Title: Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastroesophageal Adenocarcinoma (GEA)

Clinical Trial IDs

  • ORG STUDY ID: ZWI-ZW25-201
  • NCT ID: NCT03929666

Conditions

  • HER2-expressing Gastroesophageal Adenocarcinoma

Interventions

DrugSynonymsArms
ZW25ZW25 + FP
CapecitabineZW25 + XELOX
CisplatinZW25 + FP
FluorouracilZW25 + FP
LeucovorinZW25 + FP
OxaliplatinZW25 + XELOX

Purpose

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, mFOLFOX6, or XELOX) 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.
    

Trial Arms

NameTypeDescriptionInterventions
ZW25 + XPExperimentalZW25 plus capecitabine and cisplatin
  • ZW25
  • Capecitabine
  • Cisplatin
ZW25 + FPExperimentalZW25 plus fluorouracil (5-FU), leucovorin, and cisplatin
  • ZW25
  • Cisplatin
  • Fluorouracil
  • Leucovorin
ZW25 + mFOLFOX6ExperimentalZW25 plus 5-FU, leucovorin, and oxaliplatin
  • ZW25
  • Fluorouracil
  • Leucovorin
  • Oxaliplatin
ZW25 + XELOXExperimentalZW25 plus capecitabine and oxaliplatin
  • ZW25
  • Capecitabine
  • Oxaliplatin

Eligibility Criteria

        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
                  or central 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 first study treatment dosing;
             and/or treatment with other cancer therapy, not otherwise specified in the exclusion
             criteria, within 4 weeks before the first dose of ZW25

          -  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

          -  Prior or concurrent malignancy whose natural history or treatment has the potential to
             interfere with the safety or efficacy assessment of the investigational regimen.

          -  Active hepatitis B or hepatitis C infection or other known chronic liver disease or
             infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with
             well controlled HIV [e.g., CD4>350/mm3 and undetectable viral load] are eligible.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs) (Part 1)
Time Frame:Up to 6 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective response rate (ORR) (Part 1)
Time Frame:Up to 10 months
Safety Issue:
Description: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
Measure:Disease control rate (Parts 1 and 2)
Time Frame:Up to 10 months
Safety Issue:
Description: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
Measure:Duration of response (Parts 1 and 2)
Time Frame:Up to 2 years
Safety Issue:
Description:Median duration of response (in months) and range (minimum, maximum)
Measure:Progression-free survival (Parts 1 and 2)
Time Frame:Up to 2 years
Safety Issue:
Description:Median progression-free survival (in months) and range (minimum, maximum)
Measure:Overall survival (Parts 1 and 2)
Time Frame:Up to 2 years
Safety Issue:
Description:Median overall survival (in months) and range (minimum, maximum)
Measure:Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2)
Time Frame:Up to 11 months
Safety Issue:
Description:Number of participants who develop ADAs
Measure:End of infusion concentration of ZW25 (Parts 1 and 2)
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Maximum serum concentration of ZW25 (Parts 1 and 2)
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Trough concentration of ZW25 (Parts 1 and 2)
Time Frame:Up to 11 months
Safety Issue:
Description:
Measure:Incidence of adverse events (Part 2)
Time Frame:Up to 11 months
Safety Issue:
Description:Number of participants who experienced an adverse event
Measure:Incidence of lab abnormalities (Part 2)
Time Frame:Up to 11 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zymeworks Inc.

Trial Keywords

  • HER2
  • Bispecific antibody
  • Biparatopic antibody
  • Immunotherapy
  • Gastric cancers
  • Esophageal cancers
  • Gastroesophageal junction (GEJ) cancers
  • Chemotherapy
  • XP
  • FP
  • mFOLFOX6
  • Capecitabine
  • Cisplatin
  • 5-FU
  • Leucovorin (folinic acid)
  • Oxaliplatin
  • XELOX

Last Updated

December 12, 2019