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HER2-expressing CancersPhase 1/2NCT05027139

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

A Phase 1/2 study testing Zanidatamab and Evorpacept in people with HER2-expressing Cancers, run by Jazz Pharmaceuticals at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2-expressing Cancers
What is being tested?
Zanidatamab and Evorpacept
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
11 sitesUnited States
Study dates
15 Sep 2021to 30 Sep 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Astera Cancer Care

    East Brunswick, New Jersey, 08816

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • UC San Diego - Moores Cancer Center

    La Jolla, California, 92093

  • UCLA Department of Medicine Hematology/Oncology

    Los Angeles, California, 90095

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53792

  • UC Irvine Health - Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Magee-Womens Hospital of UPMC

    Pittsburgh, Pennsylvania, 15213

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Northwest Medical Specialties, PLLC

    Tacoma, Washington, 98405

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Zanidatamab, Evorpacept
Keywords
JZP598

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanidatamabDrug

    Also called ZW25, JZP598, ZIIHERA®

    Administered intravenously (IV)

  • EvorpaceptDrug

    Also called ALX148

    Administered IV

Study groups in NCT05027139
Study groupRoleWhat they receive
Zanidatamab plus evorpacept (ALX148)ExperimentalNot described
Receives: Drug: Zanidatamab; Drug: Evorpacept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicities (DLTs; Part 1)

    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)

    Measured: Up to 4 weeks

  2. Incidence of AEs (Part 1)

    Number of patients who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs)

    Measured: Up to 7 months

  3. Incidence of clinical laboratory abnormalities (Part 1)

    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

    Measured: Up to 7 months

  4. Confirmed objective response rate (ORR)(Part 2)

    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

    Measured: Up to 2 years

Secondary outcomes (11)

  1. Disease control rate (DCR)(Part 2)

    Number of patients who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1

    Measured: Up to 2 years

  2. Clinical benefit rate (CBR)(Part 2)

    Number of patients who achieved a SD for ≥ 24 weeks or a confirmed BOR of CR or PR during treatment per RECIST 1.1

    Measured: Up to 2 years

  3. Duration of response (DOR)(Part 2)

    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

    Measured: Up to 2 years

  4. Progression-free survival (PFS)(Part 2)

    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

    Measured: Up to 2 years

  5. Progression-free survival 6 (PFS6)(Part 2)

    Number of patients with a PFS time ≥ 24 weeks

    Measured: Up to 6 months

  6. Overall survival (OS)(Part 2)

    The time from first dose of study treatment until death from any cause

    Measured: Up to 2 years

  7. Incidence of AEs (Part 2)

    Number of patients who experienced AEs, SAEs, or AESIs

    Measured: Up to 7 months

  8. Incidence of clinical laboratory abnormalities (Part 2)

    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

    Measured: Up to 7 months

  9. Maximum serum concentration of zanidatamab and evorpacept (ALX148) (Part 2)

    Measured: Up to 7 months

  10. Trough concentration of zanidatamab and evorpacept (ALX148) (Part 2)

    Minimum observed serum concentration (trough)

    Measured: Up to 7 months

  11. Incidence of anti-drug antibodies (ADAs)(Part 2)

    Number of patients who develop ADAs

    Measured: Up to 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2021
  2. Study start15 Sep 2021
  3. Primary completion29 Aug 2025
  4. Study completion30 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
single-arm, open-label, multi-cohort, multi-center study
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05027139
Sponsor's protocol ID
ZWI-ZW25-204
Status last verified
Jun 2026
First submitted
23 Aug 2021
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Zanidatamab and Evorpacept in people with HER2-expressing Cancers, run by Jazz Pharmaceuticals at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs; Part 1) (time frame: Up to 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05027139.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.

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