Zanidatamab for Early Stage HER2 Positive Breast Cancer

Overseen By Vicente Valero, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Concurrent malignancy, Cardiac disease, Hepatitis, 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: 6

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called zanidatamab for individuals with early-stage HER2-positive breast cancer, a type of cancer that grows due to the HER2 protein. The main goal is to determine zanidatamab's effectiveness in treating this condition. This trial may suit individuals whose breast cancer tumors measure between 1 and 3 cm, have not spread, and who are open to surgery if needed. Participants must be in good overall health and willing to follow the study's guidelines. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like corticosteroids or have conditions requiring specific medications, you might need to adjust or stop them. It's best to discuss your current medications with the trial team.

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

Research has shown that zanidatamab is generally safe and well-tolerated. It has demonstrated promising results in treating various HER2-positive cancers, including breast, biliary tract, stomach, and lung cancers. Specifically, combining zanidatamab with chemotherapy for HER2-positive metastatic breast cancer has shown early signs of effectiveness and manageable side effects.

One study found that using zanidatamab with other cancer drugs like palbociclib and fulvestrant was generally safe and showed promise in fighting tumors. Additionally, combining zanidatamab with docetaxel (a chemotherapy drug) showed activity against advanced HER2-positive breast cancer, again with manageable side effects.

These studies suggest that zanidatamab is well-tolerated by patients, with side effects considered manageable. However, while these findings are promising, further study is necessary to ensure its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zanidatamab is unique because it targets the HER2 protein differently than current treatments like trastuzumab and pertuzumab. Unlike these standard treatments, zanidatamab is a bispecific antibody, which means it can bind to two sites on the HER2 protein simultaneously, potentially enhancing its anti-tumor activity. Researchers are excited about zanidatamab because this dual-targeting approach might provide a more effective option for patients with early-stage HER2-positive breast cancer, offering hope for better outcomes and fewer side effects.

What evidence suggests that zanidatamab might be an effective treatment for early stage HER2+ breast cancer?

Research has shown that zanidatamab, the investigational treatment in this trial, holds promise for treating HER2-positive cancers, such as breast cancer. It effectively shrinks or eliminates tumors and helps patients live longer without cancer progression. Studies have also found that zanidatamab, when combined with chemotherapy, maintains its effectiveness over time. This treatment targets the HER2 protein, which is often overly active in some cancers, helping to halt cancer growth and spread. These findings suggest zanidatamab could be effective for early-stage HER2-positive breast cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Vicente Valero, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early stage, low risk HER2+ breast cancer. Participants must have normal organ and marrow function, no prior BC treatments or other malignancies that could affect the study, and be able to consent. They should not be pregnant or breastfeeding and must use contraception if of reproductive potential.

Inclusion Criteria

My tumor is between 1 and 3 cm, with no spread to lymph nodes or other parts.

I am older than 18 years.

My heart's pumping ability is normal as shown by a recent heart scan.

Exclusion Criteria

Your heart's electrical activity (QT interval) is too long.

I have received some form of treatment for my current breast cancer diagnosis.

I do not have serious heart problems like recent heart attacks or uncontrolled high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanidatamab by vein every 2 weeks for up to 6 doses

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zanidatamab

Trial Overview The trial tests Zanidatamab's effectiveness in treating early stage HER2+ breast cancer by looking at the complete response after treatment. It's a single-arm study where all participants receive Zanidatamab along with standard care drugs Tamoxifen or Letrozole.

How Is the Trial Designed?

Group I: Zanidatamab Experimental Treatment 3 Interventions

zanidatamab by vein every 2 weeks (+/- 3 days) for up to 6 doses (3 study cycles

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Zymeworks BC Inc.

Industry Sponsor

Trials

6

Recruited

1,300+

Zymeworks Inc.

Industry Sponsor

Trials

11

Recruited

2,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11871714/

Exploring Zanidatamab's efficacy across HER2-positive ... In summary, zanidatamab has shown significant tumor response, progression-free survival, disease control, and improved quality of life in early ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07102381

NCT07102381 | A Phase 2 Neoadjuvant Study of ... The purpose of this study is to see if zanidatamab is safe and effective, when combined with chemotherapy, in treating people who has Human Epidermal Growth ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4013

4-year follow-up of a phase 2 trial. After a median 4-year follow-up, zani + chemo demonstrated clinically meaningful efficacy in the 1L treatment of HER2+ mGEA, with durable responses and a ...

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

Zanidatamab (zani), a HER2-targeted bispecific antibody, ... Background: HER2-targeted agents have improved outcomes in HER2-positive breast cancer, but some pts develop resistance, relapse, or do not respond to ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40025472/

Exploring Zanidatamab's efficacy across HER2-positive ... In summary, zanidatamab has shown significant tumor response, progression-free survival, disease control, and improved quality of life in ...

6. 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.

7. 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 ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204525001408

Zanidatamab plus palbociclib and fulvestrant in previously ... Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy- ...