Zanidatamab + Evorpacept for Advanced HER2-Expressing Cancer

No longer recruiting at 14 trial locations

Overseen By Bruno Fang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jazz Pharmaceuticals

Must not be taking: Anti-CD47, Anti-SIRPα

Disqualifiers: Invasive malignancy, Brain metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining zanidatamab and evorpacept (also known as ALX148, an experimental treatment) is safe and effective for treating cancers that express HER2, a protein linked to aggressive cancer growth. It targets individuals with advanced HER2-expressing cancers, such as certain types of breast or stomach cancer, whose cancer has progressed despite other treatments. Ideal participants have measurable disease and are willing to undergo a new biopsy for testing. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you have not received systemic anticancer therapy within 4 weeks before starting the study treatment. If you are on such medications, you may need to stop them before joining the trial.

Is there any evidence suggesting that zanidatamab and evorpacept are likely to be safe?

Research has shown that the combination of zanidatamab and evorpacept is generally well-tolerated in people with HER2-expressing cancers. In earlier studies, patients experienced positive safety outcomes. Evorpacept, which blocks a protein called CD47, has been safely used with zanidatamab in patients who have already tried other treatments.

Zanidatamab has demonstrated good results in treating various HER2-positive cancers, such as breast and stomach cancers. Some patients reported mild to moderate side effects, but these were manageable. While there are some risks, the treatment has been considered safe for many patients in the trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Zanidatamab plus evorpacept is unique because it targets HER2-expressing cancers in a novel way. Most treatments for HER2-positive cancers, like trastuzumab and pertuzumab, focus on blocking HER2 receptors to stop tumor growth. However, this combination leverages zanidatamab's ability to bind to two different parts of the HER2 protein, enhancing its effectiveness. Additionally, evorpacept is designed to improve the immune system's response by preventing cancer cells from evading immune detection. Researchers are excited about this approach because it offers a potentially more powerful attack against cancer cells, possibly leading to better outcomes for patients with advanced HER2-expressing cancers.

What evidence suggests that zanidatamab plus evorpacept could be effective for advanced HER2-expressing cancer?

This trial will evaluate the combination of zanidatamab and evorpacept for treating advanced cancers that express the HER2 protein. Research has shown that zanidatamab effectively treats several types of HER2-positive cancers, such as breast, stomach, and lung cancers. When combined with evorpacept, the treatment may more effectively target cancer cells. Previous studies demonstrated that patients with heavily treated HER2-positive cancer benefited from evorpacept, as it helps the immune system fight cancer by blocking a protein called CD47. These findings suggest that this treatment could help patients with advanced cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Elaina Gartner, MD

Principal Investigator

Zymeworks Inc.

Phoebe Harvey, MD

Principal Investigator

Zymeworks BC Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-expressing cancers, including breast and gastroesophageal cancer. Participants must have had prior treatments, an ECOG performance status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but ambulatory), measurable disease, and adequate organ function. They cannot join if they've had recent heart issues, certain other cancers, uncontrolled diseases like pancreatitis or hepatitis, HIV unless well-controlled, brain metastases that are untreated or recently treated.

Inclusion Criteria

My heart's left ventricle pumps well, with an efficiency of 50% or more.

My advanced cancer has worsened despite treatment.

My cancer is advanced, cannot be removed by surgery, and is HER2 positive.

Exclusion Criteria

I do not have another cancer that could affect this treatment's safety or results.

I have active hepatitis.

I do not have severe pancreatitis or advanced liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety and Tolerability

Evaluation of safety, tolerability, and establishment of recommended doses of zanidatamab in combination with evorpacept (ALX148)

Up to 7 months

Part 2: Anti-tumor Activity

Evaluation of anti-tumor activity of the combination of zanidatamab plus evorpacept (ALX148) at the recommended dose levels

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• ALX148
• Evorpacept
• Zanidatamab

Trial Overview The study tests the safety and effectiveness of zanidatamab combined with evorpacept in treating advanced HER2-expressing cancers. Zanidatamab targets proteins on cancer cells to stop growth while evorpacept helps the immune system attack the cancer.

How Is the Trial Designed?

Group I: Zanidatamab plus evorpacept (ALX148) Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Zymeworks Inc.

Lead Sponsor

Trials

11

Recruited

2,400+

ALX Oncology Inc.

Industry Sponsor

Trials

9

Recruited

1,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05027139

A Study of Zanidatamab (ZW25) With Evorpacept (ALX148) ... 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 [ ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/PS8-09/753445/Abstract-PS8-09-Zanidatamab-in-combination-with

Abstract PS8-09: Zanidatamab in combination with evorpacept ... Here, we report results from a phase 1b/2 trial of zani + evo in advanced HER2-expressing cancers. Methods: This two-part, open-label ...

3. alxoncology.com alxoncology.com/wp-content/uploads/2025/01/SABCS-2024-Zani-Evorpacept-Montero-Dec24.pdf

A Phase 1b/2 Study of Evorpacept plus Zanidatamab in ... ... HER2-expressing breast cancer and other cancers. Methods. • Part 1 objective: Evaluated safety, tolerability, and recommended doses for the ...

4. ir.alxoncology.com ir.alxoncology.com/news-releases/news-release-details/alx-oncology-announces-new-data-demonstrating-evorpacept

Release Details "These data suggest that HER2-positive patients whose cancer has been heavily pretreated may benefit from CD47 inhibition via evorpacept's ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871714/

Exploring Zanidatamab's efficacy across HER2-positive ... Zanidatamab has shown promising clinical outcomes in several HER2-positive cancers, including biliary tract, breast, gastric, and lung cancers.