A Dose Finding Study of ZW49 in Patients With HER2-Positive Cancers

NCT03821233 | Completed Phase 1 FDA Drug

• 1 other identifier: ZWI-ZW49-101
• Study Type: interventional
• Target: 112
• Locations: 4 countries
• Sites: 16

Brief Summary

This is a first-in-human, Phase 1, multicenter, open-label, dose-escalation study to establish the maximum-tolerated dose (MTD) or recommended dosage (RD) of ZW49, the investigational agent under study, and to assess the safety and tolerability of ZW49. Eligible patients include those with locally advanced (unresectable) or metastatic HER2-expressing cancers.

Conditions

HER2-expressing Cancers

Keywords

HER2; Bispecific antibody; Biparatopic antibody; Immunotherapy; Gastric cancers; Esophageal cancers; Gastroesophageal junction (GEJ) cancers; Breast cancer; Ovarian cancer; Non-small cell lung cancer; Colorectal cancer; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (5)

• Incidence of dose-limiting toxicities (DLTs)

  Number of participants who experienced a DLT. DLTs are events that occur following administration of any amount of ZW49 and are considered related to ZW49 per the investigator. DLTs will include only events considered related to ZW49.

  Up to 4 weeks

• Incidence of adverse events

  Number of participants who experienced an adverse event

  Up to 7 months

• Incidence of lab abnormalities

  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.

  Up to 7 months

• Incidence of electrocardiogram (ECG) and left ventricular ejection fraction (LVEF) abnormalities

  Number of participants who experienced an abnormal ECG or LVEF

  Up to 7 months

• Incidence of dose reductions of ZW49

  Number of doses reduced and number of participants who require a dose reduction

  Up to 7 months

Secondary Outcomes (6)

• Serum concentrations of ZW49

  Up to 7 months

• Incidence of anti-drug antibodies (ADAs)

  Up to 7 months

• Objective response rate (ORR)

  Up to 6 months

• Disease control rate

  Up to 6 months

• Duration of response

  Up to 2 years

Study Arms (1)

ZW49

EXPERIMENTAL

Drug: ZW49

Interventions

ZW49 DRUG

* Dose Escalation: ZW49 administered intravenously at dose levels determined by the SMC * Expansion: MTD or RD identified in the dose-escalation part of the study

ZW49

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically-confirmed diagnosis of breast cancer, gastroesophageal adenocarcinoma (GEA), or other HER2-expressing cancer with evidence of locally advanced (unresectable) and/or metastatic disease.
• Dose-escalation (Cohort 1): HER2-high advanced solid tumors
• Expansion (Cohort 2): HER2-high breast cancer
• Expansion (Cohort 3): HER2-high GEA
• Expansion (Cohort 4): HER2-high other non-breast and non-GEA cancers
• Progressive disease that has progressed on or been refractory to all standard of care. Patients who were intolerant to or ineligible for standard therapy may be eligible if the reasons are carefully documented and approval is provided by the sponsor medical monitor
• Patients with HER2-high breast cancer must have received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1)
• Patients with HER2-high GEA must have received prior treatment with trastuzumab
• Sites of disease assessible per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Dose-escalation: measurable or non-measurable disease
• Expansion: 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

You may not qualify if:

• History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure (CHF)
• Clinically significant infiltrative pulmonary disease not related to lung metastases
• Active hepatitis B or hepatitis C infection or other known chronic liver disease
• Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
• Known history of human immunodeficiency virus (HIV) infection
• Brain metastases: Untreated CNS metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as patients who are off steroids and anticonvulsants and are stable for at least 1 month at the time of screening).
• Known leptomeningeal disease (LMD)

Sponsors & Collaborators

• Zymeworks BC Inc.: lead

Study Sites (16)

City of Hope

Duarte, California, 91010, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Flinders Medical Centre

Adelaide, 5042, Australia

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Joseph Woolery, PharmD, BCOP

  Zymeworks BC Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 29, 2019
• Study Start: April 15, 2019
• Primary Completion: September 27, 2024
• Study Completion: October 8, 2024
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5); US (8); CA (2); AU (1)