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

NCT05027139 | Completed Phase 1 FDA Drug

• 1 other identifier: ZWI-ZW25-204
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

HER2-expressing Cancers

Keywords

JZP598

Outcome Measures

Primary Outcomes (4)

• 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)

  Up to 4 weeks

• Incidence of AEs (Part 1)

  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)

  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)

  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 Outcomes (11)

• Disease control rate (DCR)(Part 2)

  Up to 2 years

• Clinical benefit rate (CBR)(Part 2)

  Up to 2 years

• Duration of response (DOR)(Part 2)

  Up to 2 years

• Progression-free survival (PFS)(Part 2)

  Up to 2 years

• Progression-free survival 6 (PFS6)(Part 2)

  Up to 6 months

Study Arms (1)

Zanidatamab plus evorpacept (ALX148)

EXPERIMENTAL

Drug: Zanidatamab; Drug: Evorpacept

Interventions

Zanidatamab DRUG

Administered intravenously (IV)

Also known as: ZW25, JZP598, ZIIHERA®

Zanidatamab plus evorpacept (ALX148)

Evorpacept DRUG

Administered IV

Also known as: ALX148

Zanidatamab plus evorpacept (ALX148)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• ALX Oncology Inc.: collaborator

Study Sites (11)

UC San Diego - Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Department of Medicine Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

zanidatamab; ALX148

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: single-arm, open-label, multi-cohort, multi-center study

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: August 30, 2021
• Study Start: September 15, 2021
• Primary Completion: July 7, 2025
• Study Completion: September 30, 2025
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (11)