Zanidatamab for Breast Cancer

Recruiting at 27 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jazz Pharmaceuticals

Must be taking: Trastuzumab deruxtecan

Must not be taking: Antineoplastics, Zanidatamab

Disqualifiers: Leptomeningeal disease, Cardiovascular, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2.5 years

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zanidatamab to determine its effectiveness and safety for patients with certain types of breast cancer. Researchers aim to evaluate zanidatamab for patients whose tumors exhibit high levels of the HER2 protein. It targets individuals with advanced breast cancer who have tried other therapies but require new options. Those with breast cancer characterized by HER2 overexpression and who have already received other HER2-targeted treatments might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that zanidatamab is likely to be safe for humans?

Previous studies have shown that zanidatamab has a manageable and tolerable safety profile. While some side effects may occur, they are usually not serious and can be effectively managed. Research indicates that zanidatamab maintains this manageable safety profile when combined with other treatments like docetaxel. This finding reassures prospective trial participants, suggesting that zanidatamab is generally well-tolerated in patients with HER2-expressing cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zanidatamab is unique because it targets two specific sites on the HER2 protein, which is often overexpressed in certain breast cancers. Unlike the standard treatments for HER2-positive breast cancer, such as trastuzumab or pertuzumab, which each bind to a single site, zanidatamab's dual-targeting approach may offer a more effective blockade of the cancer-promoting signals. Researchers are excited about this innovative mechanism of action because it has the potential to improve outcomes for patients who have not responded well to existing HER2-targeted therapies.

What evidence suggests that zanidatamab might be an effective treatment for breast cancer?

Research has shown that zanidatamab, which participants in this trial will receive, yields promising results in treating HER2-positive cancers, such as breast cancer. In earlier studies, zanidatamab combined with chemotherapy helped shrink tumors in patients with HER2-positive metastatic breast cancer. The combination of zanidatamab and docetaxel (a chemotherapy drug) proved effective as an initial treatment for advanced HER2-positive breast cancer. Importantly, patients generally tolerated these treatments well, with manageable side effects. Overall, zanidatamab has demonstrated potential in targeting and combating tumors with high levels of HER2. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Zanidatamab

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

Atezolizumab, combined with nab-paclitaxel, significantly improves progression-free survival and overall survival in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC), as demonstrated in the IMpassion 130 trial.

The FDA and EMA approvals of atezolizumab represent a major advancement in treating metastatic TNBC, but further research is needed to identify better biomarkers for response and strategies to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of breast cancer. Reddy, SM., Carroll, E., Nanda, R.[2021]

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]

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]

The management of metastatic breast cancer (MBC) is increasingly personalized, focusing on individual tumor characteristics and patient history to optimize treatment efficacy and quality of life.

Promising advancements include dual targeting strategies for estrogen receptor-positive breast cancer and the use of PARP inhibitors for BRCA mutant cases, while challenges remain in identifying effective treatments for triple-negative breast cancer and managing toxicity in targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in treatment stratification for metastatic breast cancer. Barton, S., Swanton, C.[2021]

The Phase III DESTINY-Breast04 trial demonstrated that trastuzumab deruxtecan (T-DXd) significantly improves survival in patients with HER2-negative metastatic breast cancer, including those with low HER2 expression, which was previously thought to be untreatable.

This trial is prompting a reevaluation of treatment strategies for HER2-low breast cancer, highlighting the need for ongoing clinical trials to address emerging challenges and evidence gaps in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting HER2-low in metastatic breast cancer: an evolving treatment paradigm. Yang, C., Brezden-Masley, C., Joy, AA., et al.[2023]

Atezolizumab combined with nab-paclitaxel has been approved for the first-line treatment of PD-L1-positive metastatic triple-negative breast cancer (TNBC), showing significant clinical benefits based on the IMpassion130 trial results.

This combination therapy has a favorable risk-benefit profile, but ongoing research is necessary to discover better predictive biomarkers for treatment response and to explore new immunotherapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in the treatment of metastatic triple-negative breast cancer. Pérez-García, J., Soberino, J., Racca, F., et al.[2021]

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]

Trastuzumab has significantly improved outcomes for patients with HER2-positive breast cancer, making their survival rates comparable to those with luminal tumors, and the current first-line treatment involves a combination of pertuzumab and trastuzumab with a taxane.

Newly approved drugs like tucatinib and trastuzumab deruxtecan offer promising options for patients whose cancer has progressed after standard treatments, highlighting the need for personalized treatment strategies and understanding drug resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic breast cancer: a comprehensive review. Exman, P., Tolaney, SM.[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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41202501/

results from an open-label, multicenter, phase Ib/II study Conclusion: Zanidatamab demonstrated efficacy and a manageable and tolerable safety profile with docetaxel as first-line treatment in patients ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-13749-1

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.

3. asco.org asco.org/abstracts-presentations/ABSTRACT362062

Zanidatamab (zani), a HER2-targeted bispecific antibody, ... Conclusions: Zani and docetaxel combination demonstrated antitumor activity in 1L therapy for advanced HER2+ breast cancer, with a manageable safety profile.

4. onclive.com onclive.com/view/zanidatamab-chemotherapy-yields-responses-and-is-safe-in-her2-expressing-metastatic-breast-cancer

Zanidatamab/Chemotherapy Yields Responses and Is ... Zanidatamab/chemotherapy showed early antitumor activity with a manageable safety profile in patients with HER2-expressing metastatic breast cancer.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02892123

NCT02892123 | Trial of ZW25 (Zanidatamab) in Patients ... This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 (zanidatamab) by itself and combined with selected ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04224272

NCT04224272 | A Study of ZW25 (Zanidatamab) With ... This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) in ...

7. esmoopen.com esmoopen.com/article/S2059-7029(25)01721-1/fulltext

Zanidatamab in combination with docetaxel in first-line ... Zanidatamab demonstrated efficacy and a manageable and tolerable safety profile with docetaxel as first-line treatment in patients with HER2- ...