A Study of Zanidatamab (ZW25) With Evorpacept (ALX148) in Patients With Advanced HER2-expressing Cancer

June 29, 2026 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
No longer available

No longer available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UC San Diego - Moores Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine Hematology/Oncology
      • Orange, California, United States, 92868
        • UC Irvine Health - Chao Family Comprehensive Cancer Center
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Astera Cancer Care
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee-Womens Hospital of UPMC
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
    • Washington
      • Tacoma, Washington, United States, 98405
        • NorthWest Medical Specialties, PLLC
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin - Madison

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Zanidatamab plus evorpacept (ALX148)
Drug: Zanidatamab
Administered intravenously (IV)
Other Names:
  • ZW25
  • JZP598
  • ZIIHERA®
Drug: Evorpacept
Administered IV
Other Names:
  • ALX148

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Number of patients with a PFS time ≥ 24 weeks
Up to 6 months
Overall survival (OS)(Part 2)
Time Frame: Up to 2 years
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jazz Pharmaceuticals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ALX Oncology Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 29, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZWI-ZW25-204

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com

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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