Zanidatamab + Chemotherapy for Breast Cancer

(EmpowHER 208 Trial)

Recruiting at 12 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jazz Pharmaceuticals

Must not be taking: Chemotherapy, Anti-HER2 therapy

Disqualifiers: Stage IV cancer, Bilateral cancer, 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: 8 months

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether zanidatamab is safe and effective when combined with chemotherapy for treating early-stage HER2-positive breast cancer, a type that grows faster and spreads more easily. It compares different treatment combinations, including zanidatamab with two chemotherapy options and a standard treatment combination. Suitable participants have stage II or III HER2-positive breast cancer and plan to undergo breast surgery after treatment. The trial aims to find better ways to treat breast cancer and improve patient outcomes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that zanidatamab, when combined with chemotherapy, is generally safe and manageable for patients. Studies have tested zanidatamab with various chemotherapy drugs, such as docetaxel and paclitaxel, and found that patients tolerated these combinations well. No severe side effects halted treatment, indicating the doses were safe. In earlier studies, patients with HER2-positive breast cancer, the same type targeted in this trial, tolerated the treatment without major safety issues. This suggests that zanidatamab, along with chemotherapy, is generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Zanidatamab is unique because it targets the HER2 receptor in a new way, potentially offering a more effective approach for treating HER2-positive breast cancer. Unlike standard treatments like trastuzumab and pertuzumab, which also target HER2, zanidatamab is a bispecific antibody. This means it can bind to two different sites on the HER2 receptor, potentially enhancing its cancer-fighting capabilities. Researchers are excited about zanidatamab because this dual targeting might lead to improved outcomes for patients, offering new hope in the battle against this aggressive form of cancer.

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

This trial will compare different treatment combinations for HER2-positive breast cancer. Studies have shown that zanidatamab, one of the treatments in this trial, achieves a high success rate when combined with the chemotherapy drugs docetaxel and carboplatin. Specifically, 90.9% of patients experienced tumor shrinkage, and 97.0% had their disease under control. Another arm of this trial will test zanidatamab with paclitaxel. Research shows this combination has an 86.4% success rate in shrinking tumors, with 90.9% of patients not experiencing cancer progression for at least six months. These findings suggest that zanidatamab, which targets the HER2 protein, effectively controls and reduces tumors in HER2-positive breast cancer. Overall, zanidatamab shows promising results when combined with different chemotherapy treatments. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with Stage II or III HER2-positive, early-stage breast cancer. Participants must have a tumor larger than 2 cm, agree to surgery after therapy, and have good heart function (LVEF ≥ 50%). They should be in decent health (ECOG status of 0 or 1) and have proper organ function.

Inclusion Criteria

My breast cancer is confirmed to be HER2-positive.

I am using effective birth control methods.

3. Has a known hormone receptor (HR) status of the primary tumor 4. Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanidatamab in combination with chemotherapy for HER2-positive breast cancer

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for event-free survival and overall survival

46 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Docetaxel
• Paclitaxel
• Pertuzumab
• Trastuzumab
• Zanidatamab

Trial Overview The study tests the safety and effectiveness of zanidatamab when combined with chemotherapy drugs like Docetaxel, Pertuzumab, Trastuzumab, Paclitaxel, and Carboplatin in treating early-stage HER2-positive breast cancer before surgery.

How Is the Trial Designed?

Group I: Zanidatamab with docetaxel and carboplatin Active Control 3 Interventions

Zanidatamab in combination with chemotherapy docetaxel and carboplatin

Group II: Trastuzumab and pertuzumab with docetaxel and carboplatin Active Control 4 Interventions

Trastuzumab and pertuzumab in combination with chemotherapy docetaxel and carboplatin

Group III: Zanidatamab with paclitaxel Active Control 2 Interventions

Zanidatamab in combination with chemotherapy paclitaxel

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+

Citations

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

results from an open-label, multicenter, phase Ib/II study The confirmed objective response rate was 90.9%, disease control rate was 97.0%, and median duration of response was 23.5 months. Median time to ...

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. 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. researchgate.net researchgate.net/publication/397323728_Zanidatamab_in_combination_with_docetaxel_in_first-line_HER2-positive_breast_cancer_results_from_an_open-label_multicenter_phase_IbII_study

results from an open-label, multicenter, phase Ib/II study Zanidatamab in combination with docetaxel in first-line HER2-positive breast cancer: results from an open-label, multicenter, phase Ib/II study.

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/5/828/745035/Co-clinical-Trial-of-Novel-Bispecific-Anti-HER2

Co-clinical Trial of Novel Bispecific Anti-HER2 Antibody ... The study demonstrated that zanidatamab was well tolerated and showed signals of activity in many tumor types. Notably, in the non-breast, non-gastric cancer ...

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

4-year follow-up of a phase 2 trial. As of July 28, 2024, the median (range) follow-up was 48 (29-59) mo; 8 pts (17%) were on zani treatment and 19 (41%) in survival follow-up.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00537-X/fulltext

319P Antitumour activity and safety of first-line ... In a safety run-in of 6 pts, no dose-limiting toxicities were identified. In 14 response-evaluable pts, the confirmed ORR was 43% (95% CI 18, 71; 1 complete ...