What side effects are associated with this type of intervention?

HER2 inhibitors, such as trastuzumab and lapatinib, commonly cause side effects including diarrhea, rash, and hepatic adverse events. CD47 blockade therapies, like evorpacept, have been associated with dose-limiting toxicities, though specific side effects are less well-documented. Broadly, cancer treatments can lead to neutropenia, fatigue, stomatitis, hypertension, and gastrointestinal issues. Patients should discuss potential side effects with their healthcare provider to manage and mitigate these risks effectively.

What prior FDA approvals exist?

The FDA has approved several drugs targeting HER2 for the treatment of HER2-expressing cancers. Notable examples include trastuzumab, pertuzumab, and ado-trastuzumab emtansine, which are used primarily in breast cancer and gastric cancer. These drugs work by inhibiting the HER2 receptor, thereby preventing cancer cell growth and proliferation. While specific FDA-approved drugs targeting CD47 are not mentioned, the combination of HER2 inhibition and immune checkpoint blockade (such as PD-1/PD-L1 inhibitors like pembrolizumab) represents a similar therapeutic strategy aimed at enhancing the immune system's ability to target cancer cells.

What other types of research exist?

Promising alternatives to Zanidatamab and Evorpacept (ALX148) for HER2-expressing cancer include: 1) Trastuzumab Deruxtecan (Enhertu), an antibody-drug conjugate targeting HER2, which has shown significant efficacy in HER2-positive cancers. 2) Tucatinib, a small molecule tyrosine kinase inhibitor that selectively inhibits HER2, often used in combination with trastuzumab and capecitabine. 3) Margetuximab, a monoclonal antibody targeting HER2, designed to enhance immune system engagement. These therapies have demonstrated promising results in clinical trials and are expected to be key options in 2024.

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Monoclonal Antibodies

Zanidatamab + Evorpacept for Advanced HER2-Expressing Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Jazz Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Progression after or during the most recent systemic regimen of treatment for advanced cancer with prior therapies including approved agents known to confer clinical benefit

Locally advanced (inoperable) and/or metastatic HER2-expressing cancer based on local or central laboratory test results

Must not have

Prior or concurrent invasive malignancy that may interfere with safety or efficacy assessment

Active hepatitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, zanidatamab and evorpacept, to see if they are safe and effective for patients with advanced HER2-expressing cancers. The treatment works by targeting cancer cells and boosting the immune system. Evorpacept has been studied for its safety, tolerability, and antitumor activity in combination with other drugs like pembrolizumab and trastuzumab.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's increased activity against cancer cells which can sometimes affect normal cells too. Specific side effects aren't listed but generally could involve fatigue, nausea, inflammation-related symptoms among others.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My advanced cancer has worsened despite treatment.

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

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am willing to have a new biopsy for HER2 testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have active hepatitis.

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I do not have severe pancreatitis or advanced liver disease.

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I haven't had a heart attack or unstable chest pain in the last 6 months.

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I have not had radiotherapy in the last 2 weeks.

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I have never been treated with anti-CD47 or anti-SIRPα drugs.

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I haven't had cancer treatment in the last 4 weeks (or 6 weeks for certain drugs).

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My cancer has spread to the lining of my brain and spinal cord.

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I have had a stem cell transplant from a donor.

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I have brain metastases that are either untreated or causing symptoms.

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My HIV infection is well controlled.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Confirmed objective response rate (ORR)(Part 2)

Incidence of AEs (Part 1)

Incidence of clinical laboratory abnormalities (Part 1)

+1 more

Secondary study objectives

Clinical benefit rate (CBR)(Part 2)

Disease control rate (DCR)(Part 2)

Duration of response (DOR)(Part 2)

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Zanidatamab plus evorpacept (ALX148)Experimental Treatment2 Interventions

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Zanidatamab is a bispecific antibody that targets HER2, a protein overexpressed in some cancers, leading to inhibition of tumor growth and survival. Evorpacept (ALX148) is a CD47 blocker that prevents cancer cells from evading the immune system by inhibiting the 'don't eat me' signal, thereby promoting their destruction by immune cells. These mechanisms are crucial for cancer patients as they offer targeted approaches to disrupt cancer cell proliferation and enhance immune-mediated tumor clearance, potentially leading to more effective and less toxic treatments compared to traditional chemotherapy.

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