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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.

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 Intervention/treatment Phase
HER2-expressing Gastroesophageal Adenocarcinoma Drug: ZW25 Drug: Capecitabine Drug: Cisplatin Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin 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, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 91 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 10, 2019
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 + 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 + 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




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.



Information from the National Library of Medicine

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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)
    • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929666


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

Locations
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United States, Florida
H. Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Rutika Mehta, MD         
Sponsors and Collaborators
Zymeworks Inc.
Investigators
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Study Director: Rose Lai, MD, MS Zymeworks Inc.

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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: April 29, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Zymeworks Inc.:
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

Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cisplatin
Capecitabine
Oxaliplatin
Fluorouracil
Antibodies
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents