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Drug Interventions

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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/27/2021.

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

Clinicaltrials.gov identifier NCT03929666

Recruitment Status Recruiting

First Posted April 29, 2019

Last update posted June 18, 2020

Study Description

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.

  • Condition or Disease:HER2-expressing Gastroesophageal Adenocarcinoma
  • Intervention/Treatment: Drug: ZW25
    Drug: Capecitabine
    Drug: Cisplatin
    Drug: Fluorouracil
    Drug: Leucovorin
    Drug: Oxaliplatin
  • Phase: Phase 2
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 115 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastroesophageal Adenocarcinoma (GEA)
  • Actual Study Start Date: April 2019
  • Estimated Primary Completion Date: February 2022
  • Estimated Study Completion Date: January 2023
Arms and interventions
Arm Intervention/treatment
Experimental: ZW25 + FP
ZW25 plus fluorouracil (5-FU), leucovorin, and cisplatin
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: Cisplatin
Administered IV

Drug: Fluorouracil
Administered IV

Drug: Leucovorin
Administered IV
Experimental: ZW25 + XELOX
ZW25 plus capecitabine and oxaliplatin
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: Oxaliplatin
Administered IV
Experimental: ZW25 + XP
ZW25 plus capecitabine and cisplatin
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
Experimental: ZW25 + mFOLFOX6
ZW25 plus 5-FU, leucovorin, and oxaliplatin
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: Fluorouracil
Administered IV

Drug: Leucovorin
Administered IV

Drug: Oxaliplatin
Administered IV
Outcome Measures
  • Primary Outcome Measures: 1. 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.
  • 2. Incidence of adverse events (Part 1) [ Time Frame: Up to 11 months ]
    Number of participants who experienced an adverse event
  • 3. 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.
  • 4. 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
  • Secondary Outcome Measures: 1. 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
  • 2. 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
  • 3. Duration of response (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median duration of response (in months) and range (minimum, maximum)
  • 4. Progression-free survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median progression-free survival (in months) and range (minimum, maximum)
  • 5. Overall survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]
    Median overall survival (in months) and range (minimum, maximum)
  • 6. Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) [ Time Frame: Up to 11 months ]
    Number of participants who develop ADAs
  • 7. End of infusion concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • 8. Maximum serum concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • 9. Trough concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
  • 10. Incidence of adverse events (Part 2) [ Time Frame: Up to 11 months ]
    Number of participants who experienced an adverse event
  • 11. 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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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.)

Contacts and Locations
Contacts

Contact: Zymeworks Clinical Trial Resource (206) 237-1030 medinfo@zymeworks.com

Locations
Show 15 Study Locations
Sponsors and Collaborators

Zymeworks Inc.

Investigators

Study Director: Neil Josephson, MD Zymeworks Inc.

More Information
  • Responsible Party: Zymeworks Inc.
  • ClinicalTrials.gov Identifier: NCT03929666 History of Changes
  • Other Study ID Numbers: ZWI-ZW25-201
  • First Posted: April 29, 2019 Key Record Dates
  • Last Update Posted: June 18, 2020
  • Last Verified: June 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Undecided
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Zymeworks Inc.: XP
    HER2
    Bispecific antibody
    Biparatopic antibody
    Immunotherapy
    Gastric cancers
    Esophageal cancers
    Gastroesophageal junction (GEJ) cancers
    Chemotherapy
    FP
    mFOLFOX6
    Capecitabine
    Cisplatin
    5-FU
    Leucovorin (folinic acid)
    Oxaliplatin
    XELOX
  • Additional relevant MeSH terms: Adenocarcinoma