Zanidatamab vs Trastuzumab for Breast Cancer

Recruiting at 200 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jazz Pharmaceuticals

Must not be taking: Antineoplastics, Hormonal therapies

Disqualifiers: Leptomeningeal disease, Cardiovascular, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or death, up to approximately 44 months

550 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether zanidatamab, an experimental treatment, combined with a doctor-selected chemotherapy, is more effective and safe than trastuzumab with chemotherapy for advanced HER2-positive breast cancer. It targets patients whose cancer has spread and who haven't responded well to previous treatments. The study seeks participants with HER2-positive metastatic breast cancer that has progressed after T-DXd therapy. This trial aims to offer new hope for those needing alternatives in their treatment journey. As a Phase 3 trial, it represents the final step before FDA approval, giving participants a chance to contribute to potentially groundbreaking treatment advancements.

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 had any local or systemic cancer therapy within 4 weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zanidatamab is safe in several studies involving patients with HER2-positive cancers, such as breast cancer. One study found that when zanidatamab was combined with chemotherapy, patients with advanced or spreading cancers generally tolerated it well, with no unexpected safety issues.

Trastuzumab, a well-known treatment, has been safely used for many years to treat HER2-positive breast cancer. It is FDA-approved and has a well-established safety record.

In summary, previous studies have demonstrated that both zanidatamab and trastuzumab are generally safe, with no major unexpected side effects reported for zanidatamab. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Unlike the standard treatment for HER2-positive metastatic breast cancer, which typically includes drugs like trastuzumab, zanidatamab offers a unique approach. Researchers are excited about zanidatamab because it is a bispecific antibody, meaning it can bind to two different sites on the HER2 protein, potentially leading to more effective tumor targeting and destruction. This dual-binding capability sets it apart from traditional treatments, which usually target a single site, and it could enhance efficacy in patients who have progressed on previous therapies.

What evidence suggests that this trial's treatments could be effective for metastatic HER2-positive breast cancer?

Research has shown that zanidatamab, one of the treatments in this trial, yields promising results for HER2-positive cancers, such as breast cancer. Studies have found that zanidatamab, when combined with chemotherapy, can significantly shrink tumors in patients with advanced breast cancer. Some patients have experienced long-lasting benefits from this treatment. Additionally, zanidatamab's side effects are generally manageable, making it a viable option for patients.

In this trial, another group of participants will receive trastuzumab, a well-known treatment for HER2-positive breast cancer, which has effectively helped patients live longer when used with chemotherapy. Overall, both treatments are effective, but zanidatamab might offer a new option for those who haven't responded well to other treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with HER2-positive breast cancer that's spread and who've had issues with a previous treatment called T-DXd. They need to have measurable cancer growth, be expected to live at least 6 more months, and their body functions (like blood cells, liver, kidneys) must meet certain levels.

Inclusion Criteria

My doctor believes I have at least 6 months to live.

My blood test results meet the study's requirements.

I am at least 18 years old or considered an adult by local laws.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either zanidatamab or trastuzumab in combination with physician's choice of chemotherapy

Until disease progression or death, up to approximately 44 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 44 months

Long-term Follow-up

Participants are monitored for overall survival

Up to approximately 80 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Eribulin
• Gemcitabine
• Trastuzumab
• Vinorelbine
• Zanidatamab

Trial Overview

The study compares Zanidatamab plus a chemotherapy chosen by the doctor against Trastuzumab with the same chemo options. It aims to see which combination is safer and works better for patients whose cancer has worsened after T-DXd treatment.

How Is the Trial Designed?

Group I: Zanidatamab plus physician's choice of chemotherapy Experimental Treatment 5 Interventions

Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of zanidatamab plus physician's choice of chemotherapy (eribulin, or vinorelbine, or gemcitabine, or capecitabine).

Group II: Trastuzumab plus physician's choice of chemotherapy Active Control 5 Interventions

Participants with HER2-positive metastatic breast cancer (mBC) who have progressed on, or are intolerant to, previous T-DXd treatment will be randomized to receive intravenous infusion of trastuzumab plus physician's choice of chemotherapy (eribulin, or gemcitabine, or vinorelbine, or capecitabine).

Trastuzumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in United States as Herceptin for:

• Adjuvant treatment of HER2-positive breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Canada as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Japan as Herceptin for:

• Breast cancer
• Gastric cancer

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

Published Research Related to This Trial

PF-05280014 (Trazimera™) is a biosimilar to trastuzumab that has been approved in the EU for all the same indications, including HER2-positive breast and gastric cancers, demonstrating similar efficacy and safety profiles.

Clinical studies have shown that PF-05280014 has comparable pharmacokinetic properties and tolerability to reference trastuzumab, making it an effective alternative for patients needing trastuzumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PF-05280014: A Trastuzumab Biosimilar. Paik, J.[2019]

The study evaluated the efficacy and safety of Herzuma®, a trastuzumab biosimilar, in patients with HER2+ metastatic breast cancer who had previously failed at least two HER2-targeted therapies.

Herzuma® was tested in combination with treatment of physician's choice, indicating its potential as a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study to investigate the efficacy of trastuzumab biosimilar (Herzuma®) plus treatment of physician's choice (TPC) in patients with heavily pretreated HER-2+ metastatic breast cancer (KCSG BR 18-14/KM10B). Sim, SH., Kim, JE., Kim, MH., et al.[2022]

Trastuzumab (Herceptin) is a safe and effective treatment for patients with metastatic breast cancer that overexpresses the HER2 gene, showing response rates of 11% to 23% in various phase II studies involving heavily pretreated and previously untreated patients.

The treatment is associated with a low incidence of serious side effects, primarily cardiac dysfunction syndrome in less than 5% of patients, and does not cause common chemotherapy side effects like hair loss or low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials of single-agent trastuzumab (Herceptin). Baselga, J.[2015]

T-DM1 is highly effective against HER2-positive breast cancer cell lines, including those resistant to trastuzumab and lapatinib, demonstrating strong growth inhibition in vitro and significant tumor suppression in vivo.

The mechanism of action for T-DM1 includes inducing mitotic catastrophe, a novel finding that contributes to its effectiveness, as evidenced by increased apoptosis and abnormal cell division in treated cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Barok, M., Tanner, M., Köninki, K., et al.[2021]

Trastuzumab significantly improves treatment outcomes for women with HER2 positive breast cancer, as shown in four large randomized trials.

The main safety concerns associated with trastuzumab are serious infusion-related reactions and cardiotoxicity, highlighting the need to weigh the benefits against these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. Svetlovska, D., Mardiak, J., Kristova, V.[2016]

Trastuzumab emtansine (T-DM1) is an effective antibody-drug conjugate that targets HER2, showing significant antitumor activity in patients with HER2-positive metastatic breast cancer, even in those resistant to other HER2-targeted therapies.

In clinical studies, T-DM1 demonstrated improved tolerability and efficacy compared to standard treatments, with a maximum tolerated dose of 3.6 mg/kg administered every three weeks, confirming its favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antibody-drug conjugates in oncology: from the concept to trastuzumab emtansine (T-DM1)]. Gonçalves, A., Trédan, O., Villanueva, C., et al.[2019]

In a study of 2,024 Japanese women with HER2-positive early-stage breast cancer, trastuzumab (TZM) demonstrated high efficacy, with a three-year overall survival rate of 98.9% and a disease-free survival rate of 94.2%.

The safety profile of TZM was acceptable, with only 18.8% of patients experiencing adverse events, and serious grade 3/4 adverse events were rare, occurring in just 0.6% of patients, indicating that TZM is a viable treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients. Yamshiro, H., Iwata, H., Masuda, N., et al.[2022]

Trastuzumab, a monoclonal antibody, has significantly improved the prognosis for patients with HER2 positive breast cancer, with one year of treatment now being the standard adjuvant therapy based on evaluations from over 10,000 patients in six randomized trials.

Despite its effectiveness, cardiac safety remains a concern, and there is ongoing research into shorter, less toxic treatment regimens and new anti-HER2 strategies to address issues of resistance to trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer. Guarneri, V., Barbieri, E., Dieci, MV., et al.[2018]

Trastuzumab (Herceptin) is highly effective in treating metastatic breast cancers that overexpress the HER-2/neu receptor, showing response rates comparable to traditional chemotherapy with significantly lower toxicity.

The success of trastuzumab in advanced cases has prompted ongoing clinical trials to explore its potential benefits in early-stage HER-2/neu-overexpressing breast cancer, indicating a shift towards more targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Emens, LA.[2015]

In a study of 469 patients with HER2-positive metastatic breast cancer, those who had previously received trastuzumab in the adjuvant setting (TP-group) experienced significantly worse overall survival (17 months) and time to next treatment (7 months) compared to trastuzumab-naïve patients (TN-group), who had median survival of 30 months and 13 months, respectively.

The findings suggest that prior treatment with trastuzumab may lead to resistance, resulting in diminished efficacy of subsequent trastuzumab-based therapies, highlighting the need for further research into optimizing treatment strategies for patients with a history of trastuzumab use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Palliative HER2-Targeted Therapy in HER2-Positive Metastatic Breast Cancer Is Less Effective After Previous Adjuvant Trastuzumab-Based Therapy. Rier, HN., Levin, MD., van Rosmalen, J., et al.[2018]

HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.

Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. Stanowicka-Grada, M., Senkus, E.[2023]

Trastuzumab (Herceptin) is an effective first-line treatment for metastatic breast cancer patients with HER2 overexpression/amplification, improving both disease-free and overall survival when used alone or with chemotherapy.

Despite its benefits, there are ongoing uncertainties regarding the optimal use of trastuzumab, including its safety during long-term treatment, the effectiveness of continuing treatment after disease progression, and its combination with hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspective of trastuzumab treatment. Iwata, H.[2019]

Trastuzumab (Herceptin) significantly improves outcomes for women with HER2-positive metastatic breast cancer, enhancing time to disease progression, response rates, and overall survival when added to first-line chemotherapy, as shown in randomized multicenter trials.

Recent phase III trials indicate that trastuzumab is also effective in the adjuvant setting, leading to significant improvements in disease-free and overall survival for patients with HER2-positive early-stage breast cancer, establishing it as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab: a review of its use in the management of HER2-positive metastatic and early-stage breast cancer. Plosker, GL., Keam, SJ.[2022]

Trastuzumab significantly improves survival for patients with HER2-positive breast cancer, yet a substantial number of patients do not receive this therapy, with non-receipt rates ranging from 12% in the U.S. to as high as 59.5% in various regions for early breast cancer.

Barriers to accessing trastuzumab include high treatment costs and funding issues, particularly affecting older patients and those with specific tumor characteristics; however, the introduction of safe and effective biosimilars could enhance access and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Global Need for a Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer. Blackwell, K., Gligorov, J., Jacobs, I., et al.[2019]

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