Zanidatamab for Breast Cancer

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jazz Pharmaceuticals

Must be taking: Trastuzumab deruxtecan

Must not be taking: Antineoplastics, Zanidatamab

Disqualifiers: Leptomeningeal disease, Cardiovascular, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of zanidatamab for the treatment of participants with previously treated solid tumors that have Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry (IHC) 3+ overexpression.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have been treated with systemic cancer therapies, including hormonal therapies for breast cancer, within 4 weeks or 5 half-lives before joining the trial.

What data supports the effectiveness of the drug Zanidatamab for breast cancer?

The research highlights the effectiveness of similar drugs like trastuzumab deruxtecan and trastuzumab emtansine, which target the HER2 protein in breast cancer, showing improved survival and outcomes. These findings suggest that targeting HER2, as Zanidatamab does, could be beneficial for breast cancer treatment. ^{1 2 3 4 5}

What makes the drug Zanidatamab unique for breast cancer treatment?

Zanidatamab is unique because it targets two different parts of the HER2 protein on cancer cells, which may help overcome resistance to other HER2-targeted therapies. This dual-targeting approach is different from other treatments that typically focus on a single target. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for people with certain types of cancer (like breast, stomach, lung, and others) that have a lot of HER2 protein on their cells. Participants should have tried other treatments before without success.

Inclusion Criteria

My organs are working well.

I am of childbearing age and my pregnancy test is negative.

I am willing to use two forms of birth control if I or my partner can have children.

Exclusion Criteria

I do not have any serious health or mental conditions that would stop me from receiving the study treatment.

My colorectal cancer has KRAS/NRAS or BRAF mutations.

I have had major surgery or experienced significant injury in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanidatamab treatment for HER2-expressing solid tumors

Up to 2.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Zanidatamab (Monoclonal Antibodies)

Trial Overview The study is testing the effectiveness and safety of a drug called Zanidatamab in patients whose tumors overexpress the HER2 protein and who have already undergone previous treatments.

Participant Groups

Group I: Zanidatamab treatment arm Experimental Treatment 1 Intervention

Eligible participants receiving zanidatamab treatment

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

Jazz Pharmaceuticals Ireland Limited

Industry Sponsor

Trials

2

Recruited

250+

Findings from Research

Trastuzumab emtansine (T-DM1) is an innovative antibody-drug conjugate that effectively targets HER2-positive breast cancer cells, showing improved safety and efficacy compared to standard chemotherapy in a Phase II trial.

In a Phase III trial, T-DM1 demonstrated significantly longer progression-free and overall survival in patients previously treated with trastuzumab, marking a significant advancement in targeted breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. Peddi, PF., Hurvitz, SA.[2021]

In the KEYNOTE-086 study involving 254 patients with metastatic triple-negative breast cancer, several biomarkers such as PD-L1, CD8, stromal tumor-infiltrating lymphocytes (sTILs), tumor mutational burden (TMB), and T-cell-inflamed gene expression profile (TcellinfGEP) were significantly associated with better clinical outcomes when treated with pembrolizumab.

These findings suggest that assessing these biomarkers can help identify which patients are more likely to benefit from pembrolizumab monotherapy, enhancing personalized treatment strategies for metastatic triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. Loi, S., Salgado, R., Schmid, P., et al.[2023]

The FDA has approved three antibody-drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) for advanced breast cancer (aBC), highlighting their potential effectiveness in treating this incurable disease.

Combining next-generation ADCs with ICIs shows promise for improving treatment outcomes in patients with refractory aBC, supported by ongoing trials and early efficacy and safety results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics. Saini, KS., Punie, K., Twelves, C., et al.[2022]

A systematic review of 13 studies found that first-line chemotherapy for metastatic triple-negative breast cancer (mTNBC) resulted in a modest objective response rate of 23% and a median overall survival of 17.5 months, indicating limited effectiveness.

The review highlighted a significant unmet need for better treatment options, as second-line chemotherapy showed even lower response rates (11%) and short durations of response (4.2-5.9 months), emphasizing the necessity for therapies that provide durable responses and improved safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Li, CH., Karantza, V., Aktan, G., et al.[2020]

Combination therapies, such as endocrine therapy with cyclin-dependent kinase 4/6 inhibitors, have significantly improved overall survival for patients with hormone receptor-positive metastatic breast cancer, establishing them as the standard first-line treatment.

HER2-targeted therapies, particularly the combination of pertuzumab with trastuzumab and a taxane, have shown remarkable survival benefits in HER2-positive metastatic breast cancer, while novel therapies are being developed for challenging subtypes like triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Landmark trials in the medical oncology management of metastatic breast cancer. Lu, P., Santa-Maria, CA., Ballinger, TJ., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Targeting HER2-low in metastatic breast cancer: an evolving treatment paradigm. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic breast cancer: a comprehensive review. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Recent developments in treatment stratification for metastatic breast cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in the treatment of metastatic triple-negative breast cancer. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Landmark trials in the medical oncology management of metastatic breast cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of breast cancer. [2021]