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

• ClinicalTrials.gov Identifier: NCT05027139
• Recruitment Status: Recruiting
• First Posted: August 30, 2021
• Last Update Posted: February 16, 2023
• Sponsor: Zymeworks Inc.
• Collaborator: ALX Oncology Inc.
• Information provided by (Responsible Party): Zymeworks Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HER2-expressing Cancers	Drug: Zanidatamab; Drug: Evorpacept	Phase 1; Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 93 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: single-arm, open-label, multi-cohort, multi-center study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 15, 2021
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: October 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zanidatamab plus evorpacept (ALX148)	Drug: Zanidatamab; Administered intravenously (IV); Other Name: ZW25; Drug: Evorpacept; Administered IV; Other Name: ALX148

Outcome Measures

Primary Outcome Measures :

1. 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)
2. 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)
3. 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
4. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. Progression-free survival 6 (PFS6)(Part 2) [ Time Frame: Up to 6 months ]
   Number of patients with a PFS time ≥ 24 weeks
6. Overall survival (OS)(Part 2) [ Time Frame: Up to 2 years ]
   The time from first dose of study treatment until death from any cause
7. Incidence of AEs (Part 2) [ Time Frame: Up to 7 months ]
   Number of patients who experienced AEs, SAEs, or AESIs
8. 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
9. Maximum serum concentration of zanidatamab and evorpacept (ALX148) (Part 2) [ Time Frame: Up to 7 months ]
10. Trough concentration of zanidatamab and evorpacept (ALX148) (Part 2) [ Time Frame: Up to 7 months ]
    Minimum observed serum concentration (trough)
11. Incidence of anti-drug antibodies (ADAs)(Part 2) [ Time Frame: Up to 7 months ]
    Number of patients who develop ADAs

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Zymeworks Clinical Trial Resource; (206) 237-1030; medinfo@zymeworks.com

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35233

Principal Investigator: Ahmed Elkhanany, MD

United States, California

Pacific Center Medical Center, Inc.; Recruiting

Anaheim, California, United States, 92801

Principal Investigator: Jayaram Bharadwaj, MD

UC San Diego - Moores Cancer Center; Recruiting

La Jolla, California, United States, 92093

Principal Investigator: Kay Yeung, MD, PhD

UCLA Department of Medicine Hematology/Oncology; Recruiting

Los Angeles, California, United States, 90095

Principal Investigator: Sara Hurvitz, MD

UC Irvine Health - Chao Family Comprehensive Cancer Center; Recruiting

Orange, California, United States, 92868

Principal Investigator: Ritesh Parajuli, MD

United States, Florida

Florida Cancer Specialists; Recruiting

Sarasota, Florida, United States, 34232

Principal Investigator: Manish Patel, MD

United States, Missouri

Saint Luke's Cancer Institute; Recruiting

Kansas City, Missouri, United States, 64111

Principal Investigator: Timothy Pluard, MD

United States, New Jersey

Astera Cancer Care; Recruiting

East Brunswick, New Jersey, United States, 08816

Principal Investigator: Bruno Fang, MD

United States, Ohio

University Hospitals Cleveland Medical Center; Recruiting

Cleveland, Ohio, United States, 44106

Principal Investigator: Alberto Jose Montero, MD

United States, Pennsylvania

Magee-Womens Hospital of UPMC; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Principal Investigator: Adam Brufsky, MD

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Funda Meric-Bernstam, MD

United States, Vermont

University of Vermont Medical Center; Recruiting

Burlington, Vermont, United States, 05401

Principal Investigator: Peter Kaufman, MD

United States, Washington

Northwest Medical Specialties, PLLC; Recruiting

Tacoma, Washington, United States, 98405

Principal Investigator: Jorge Chaves, MD

United States, Wisconsin

University of Wisconsin - Madison; Recruiting

Madison, Wisconsin, United States, 53792

Principal Investigator: Kari Wisinski, MD

Sponsors and Collaborators

Zymeworks Inc.

ALX Oncology Inc.

Investigators

• Study Director: Phoebe Harvey, MD; Zymeworks BC Inc.

More Information

• Responsible Party: Zymeworks Inc.
• ClinicalTrials.gov Identifier: NCT05027139
• Other Study ID Numbers: ZWI-ZW25-204
• First Posted: August 30, 2021
• Last Update Posted: February 16, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No