What is the mechanism of action of this treatment?

HER2-targeted therapies, such as the investigational agent ZW49, work by binding to the HER2 receptors on cancer cells, which are overexpressed in certain cancers like breast and gastric cancers. This binding inhibits cell proliferation and survival pathways, leading to cancer cell death. This targeted approach is significant for cancer patients as it offers a more precise treatment option, potentially reducing tumor growth and spread while minimizing damage to normal cells, thereby improving therapeutic outcomes and reducing side effects.

What side effects are associated with this type of intervention?

HER2-targeted therapies, such as trastuzumab and lapatinib, are generally well-tolerated but can cause side effects including diarrhea, rash, and hepatic adverse events. The most serious side effect is cardiac dysfunction, particularly in patients who have been treated with anthracyclines. Common side effects of chemotherapy, often used alongside targeted therapies, include nausea, vomiting, fatigue, and myelosuppression (e.g., granulocytopenia and anemia). Immunotherapy, another common cancer treatment, can lead to immune-related adverse events such as colitis, dermatitis, and endocrinopathies.

What prior FDA approvals exist?

The FDA has approved several HER2-targeted therapies for the treatment of HER2-positive cancers. Trastuzumab (Herceptin) was one of the first, targeting the HER2 receptor to inhibit cancer cell growth. Pertuzumab (Perjeta) is often used in combination with trastuzumab and chemotherapy for enhanced efficacy. Ado-trastuzumab emtansine (Kadcyla) combines trastuzumab with a cytotoxic agent to deliver targeted chemotherapy. More recently, fam-trastuzumab deruxtecan (Enhertu) has been approved for patients with metastatic HER2-positive breast cancer who have received prior anti-HER2 therapies. These treatments have significantly improved outcomes for patients with HER2-positive cancers.

What other types of research exist?

Promising novel alternatives to ZW49 for HER2-targeted therapy in cancer patients include Trastuzumab Deruxtecan, which has shown efficacy in previously treated HER2-positive breast cancer and in patients with brain metastases, and the tucatinib-trastuzumab-capecitabine regimen, which has demonstrated safety and efficacy in treating leptomeningeal metastasis in HER2-positive breast cancer. Additionally, ZHER2:342 is a small agent that may be used as an alternative or complement to trastuzumab, with potential applications in HER2 imaging and radionuclide therapy.

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Monoclonal Antibodies

ZW49 for Cancer

Phase 1

Waitlist Available

Research Sponsored by Zymeworks BC Inc.

Eligibility Criteria Checklist

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

Must have

Patients with HER2-high breast cancer must have received prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1)

ECOG performance status score of 0 or 1

Must not have

Known history of human immunodeficiency virus (HIV) infection

Clinically significant infiltrative pulmonary disease not related to lung metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ZW49, a new drug, to find the safest and most effective dose. It focuses on patients with advanced or metastatic HER2-positive cancers. The drug works by targeting and destroying cancer cells marked by the HER2 protein.

Who is the study for?

This trial is for patients with advanced HER2-positive cancers, including breast cancer and gastroesophageal adenocarcinoma (GEA), who have tried standard treatments without success or cannot tolerate them. Participants must have a confirmed diagnosis, measurable disease for certain cohorts, an ECOG performance status of 0 or 1 indicating they are fully active or restricted in physically strenuous activity but ambulatory, and adequate organ function.

What is being tested?

The study is testing ZW49 to find the highest dose patients can take without severe side effects (MTD) and to see how safe it is. It's open-label so everyone knows they're getting ZW49, and it starts by giving small doses that get bigger until they find the MTD or recommended dosage.

What are the potential side effects?

While specific side effects of ZW49 aren't listed here as this is a first-in-human study determining safety, common side effects from similar cancer drugs include nausea, fatigue, infusion reactions like fever or chills, diarrhea, low blood cell counts increasing infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I have HER2-high breast cancer and was treated with trastuzumab, pertuzumab, and T-DM1.

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I am fully active or can carry out light work.

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My cancer is advanced and cannot be removed by surgery.

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My cancer is HER2-high and advanced.

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My heart's left ventricle functions well.

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I have HER2-high stomach cancer and was treated with trastuzumab.

Exclusion Criteria

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

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I have been diagnosed with HIV.

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I have a serious lung condition not caused by cancer spread.

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

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I have been diagnosed with leptomeningeal disease.

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I have an active hepatitis B or C infection or another chronic liver disease.

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

Incidence of adverse events

Incidence of dose reductions of ZW49

Incidence of dose-limiting toxicities (DLTs)

+2 more

Secondary study objectives

Disease control rate

Duration of response

Incidence of anti-drug antibodies (ADAs)

+4 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: ZW49Experimental Treatment1 Intervention

0 / 11Eligibility 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

HER2-targeted therapies, such as the investigational agent ZW49, work by binding to the HER2 receptors on cancer cells, which are overexpressed in certain cancers like breast and gastric cancers. This binding inhibits cell proliferation and survival pathways, leading to cancer cell death. This targeted approach is significant for cancer patients as it offers a more precise treatment option, potentially reducing tumor growth and spread while minimizing damage to normal cells, thereby improving therapeutic outcomes and reducing side effects.

Current trends and future directions in the genetic therapy of human neoplastic disease.New molecular targets in malignant gliomas.