- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05027139
A Study of Zanidatamab (ZW25) With Evorpacept (ALX148) in Patients With Advanced HER2-expressing Cancer
April 25, 2024 updated by: Jazz Pharmaceuticals
A Phase 1b/2, 2-part Open-label Study to Assess the Safety and Antitumor Activity of Zanidatamab in Combination With ALX148 in Advanced HER2-expressing Cancer
This study is being done to find out if zanidatamab when given with evorpacept (ALX148) is safe and can treat patients with advanced (locally advanced [inoperable] and/or metastatic) human epidermal growth factor receptor 2 (HER2)-expressing cancer.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Part 1 of the study will first evaluate the safety and tolerability and establish the recommended doses (RDs) of zanidatamab in combination with evorpacept (ALX148).
Part 2 of the study will evaluate the anti-tumor activity of the combination of zanidatamab plus evorpacept (ALX148) at the RD levels in indication-specific expansion cohorts.
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 2
- Phase 1
Expanded Access
Available outside the clinical trial.
See expanded access record.
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Clinical Trial Disclosure & Transparency
- Phone Number: 215-832-3750
- Email: ClinicalTrialDisclosure@JazzPharma.com
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- UC San Diego - Moores Cancer Center
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Los Angeles, California, United States, 90095
- UCLA Department of Medicine Hematology/Oncology
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Orange, California, United States, 92868
- UC Irvine Health - Chao Family Comprehensive Cancer Center
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Florida
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Sarasota, Florida, United States, 34232
- Florida Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, United States, 08816
- Astera Cancer Care
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Cleveland Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- Magee-Womens Hospital of UPMC
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Texas
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Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
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Vermont
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Burlington, Vermont, United States, 05401
- University of Vermont Medical Center
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Washington
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Tacoma, Washington, United States, 98405
- Northwest Medical Specialties, PLLC
-
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin - Madison
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
Locally advanced (inoperable) and/or metastatic HER2-expressing cancer based on local or central laboratory test results as follows:
- Parts 1 and 2: HER2-positive breast cancer as defined per American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines
- Parts 1 and 2: HER2-low breast cancer (defined as immunohistochemistry [IHC] 1+ or IHC 2+; AND is currently not and has never been HER2-positive per the ASCO/CAP guidelines)
- Part 2: HER2-positive gastroesophageal adenocarcinoma as defined per the ASCO/CAP gastric cancer-specific guidelines; or other HER2-overexpressing non-breast cancers (defined as IHC 3+; or IHC 2+ and in situ hybridization [ISH]+) per the ASCO/CAP guidelines for breast cancer
Progression after or during the most recent systemic regimen of treatment for advanced cancer. For both Part 1 and Part 2, prior therapies must have included approved agents known to confer clinical benefit.
- Subjects with HER2-positive breast cancer who did not receive trastuzumab or pertuzumab due to medical contraindications will not be eligible for this study
- Subjects with HER2-low breast cancer who have received prior HER2-targeted therapy (other than trastuzumab deruxtecan, which is allowed but not required) will not be eligible for this study
- Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- Willingness to undergo a new biopsy to provide a tumor tissue for central laboratory testing of HER2 protein expression and gene amplification by IHC and ISH assays, respectively
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ functions
- Adequate cardiac left ventricular function, as defined by a left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA) obtained within 4 weeks prior to first dose of study treatment
Exclusion Criteria:
- Previous allogeneic stem cell transplant
- Prior treatment with any anti-CD47 or anti-signal regulatory protein alpha (SIRPα) agent
- Prior or concurrent invasive malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Received systemic anticancer therapy within 4 weeks of starting study treatment (6 weeks for mitomycin C or nitrosoureas). Received radiotherapy within 2 weeks of the first dose of zanidatamab/evorpacept (ALX148)
- Untreated brain metastases, symptomatic brain metastases; or radiation treatment (stereotactic radiosurgery and whole brain radiation) for brain metastases within 2 weeks of start of study treatment
- Known leptomeningeal disease
- Active hepatitis
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. (Exception: Subjects with well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] are eligible.)
- QTc Fridericia (QTcF) > 470 ms
- 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
- Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Zanidatamab plus evorpacept (ALX148)
|
Administered intravenously (IV)
Other Names:
Administered IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of dose-limiting toxicities (DLTs; Part 1)
Time Frame: Up to 4 weeks
|
Number of patients who experienced a DLT.
DLTs include specifically defined adverse events (AEs) considered to be related to zanidatamab or evorpacept (ALX148), including combination of zanidatamab with evorpacept (ALX148)
|
Up to 4 weeks
|
Incidence of AEs (Part 1)
Time Frame: Up to 7 months
|
Number of patients who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs)
|
Up to 7 months
|
Incidence of clinical laboratory abnormalities (Part 1)
Time Frame: Up to 7 months
|
Number of patients who experienced a Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry.
Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0
|
Up to 7 months
|
Confirmed objective response rate (ORR)(Part 2)
Time Frame: Up to 2 years
|
Number of patients who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate (DCR)(Part 2)
Time Frame: Up to 2 years
|
Number of patients who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
|
Up to 2 years
|
Clinical benefit rate (CBR)(Part 2)
Time Frame: Up to 2 years
|
Number of patients who achieved a SD for ≥ 24 weeks or a confirmed BOR of CR or PR during treatment per RECIST 1.1
|
Up to 2 years
|
Duration of response (DOR)(Part 2)
Time Frame: Up to 2 years
|
The time from the first objective response (CR or PR) to documented progressive disease per RECIST 1.1, clinical progression, or death within 30 days of last dose of study drug (zanidatamab and/or evorpacept [ALX148]) from any cause
|
Up to 2 years
|
Progression-free survival (PFS)(Part 2)
Time Frame: Up to 2 years
|
The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause
|
Up to 2 years
|
Progression-free survival 6 (PFS6)(Part 2)
Time Frame: Up to 6 months
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Number of patients with a PFS time ≥ 24 weeks
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Up to 6 months
|
Overall survival (OS)(Part 2)
Time Frame: Up to 2 years
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The time from first dose of study treatment until death from any cause
|
Up to 2 years
|
Incidence of AEs (Part 2)
Time Frame: Up to 7 months
|
Number of patients who experienced AEs, SAEs, or AESIs
|
Up to 7 months
|
Incidence of clinical laboratory abnormalities (Part 2)
Time Frame: Up to 7 months
|
Number of patients who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry.
Grades are defined using NCI-CTCAE, version 5.0
|
Up to 7 months
|
Maximum serum concentration of zanidatamab and evorpacept (ALX148) (Part 2)
Time Frame: Up to 7 months
|
Up to 7 months
|
|
Trough concentration of zanidatamab and evorpacept (ALX148) (Part 2)
Time Frame: Up to 7 months
|
Minimum observed serum concentration (trough)
|
Up to 7 months
|
Incidence of anti-drug antibodies (ADAs)(Part 2)
Time Frame: Up to 7 months
|
Number of patients who develop ADAs
|
Up to 7 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Phoebe Harvey, MD, Zymeworks BC Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 15, 2021
Primary Completion (Estimated)
October 31, 2024
Study Completion (Estimated)
April 30, 2025
Study Registration Dates
First Submitted
August 23, 2021
First Submitted That Met QC Criteria
August 23, 2021
First Posted (Actual)
August 30, 2021
Study Record Updates
Last Update Posted (Estimated)
April 26, 2024
Last Update Submitted That Met QC Criteria
April 25, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- ZWI-ZW25-204
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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