Zanidatamab With Chemotherapy Compared to Trastuzumab With Chemotherapy in Metastatic HER2-Positive Breast Cancer

What is the Purpose of this Study?

This study focuses on people with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). mBC is a type of breast cancer that has spread (metastasized) to other organs in the body. The purpose of the study is to learn whether an experimental drug called zanidatamab in combination with chemotherapy works better compared to trastuzumab in combination with chemotherapy. Researchers will compare zanidatamab plus physician’s choice of a chemotherapy agent (eribulin, gemcitabine, vinorelbine, or capecitabine) and trastuzumab plus physician’s choice of a chemotherapy agent (eribulin, gemcitabine, vinorelbine, or capecitabine). Zanidatamab is an antibody (protein) made in a laboratory designed to treat patients with tumors, including mBC, that express the HER2 protein. Participants will be randomly assigned to receive either zanidatamab plus chemotherapy or trastuzumab plus chemotherapy. Study procedures also include exams, questionnaires, lab work, electrocardiogram, imaging, and biopsy.

Eligibility

Participants are eligible to be included in the study only if all of the following criteria apply:
1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.
2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a sponsor-designated central laboratory
3. Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.
4. Must have received at least 2 lines of HER2-directed therapy for their metastatic disease.

Participants are eligible to be included in the study only if all of the following criteria apply:
1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.
2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a sponsor-designated central laboratory
3. Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.
4. Must have received at least 2 lines of HER2-directed therapy for their metastatic disease.
1. Prior HER2-targeted neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months of the completion of therapy will be considered a line of treatment for metastatic disease.
2. Based on the physician's choice, participants' eligibility, and institutional and local guidelines, participants may also have received post-T-DXd therapy, for example, a tucatinib-based regimen and/or T-DM1.
3. Participants must not have received more than 4 lines of HER2-directed therapy in the metastatic setting.
5. Has measurable disease per RECIST version 1.1.
6. Is eligible to receive one of the chemotherapy options listed in the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine).
7. Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol.
8. Has a life expectancy of at least 6 months, in the opinion of the investigator.
9. Has adequate hematologic parameters as defined in the protocol.
10. Has adequate hepatic function as specified in the protocol.
11. Has creatinine clearance ≥ 50 mL/minute as calculated per local institutional guidelines.
12. Has LVEF ≥ 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention.
13. Has ECOG performance status of 0 or 1.
14. Participant agrees to the following based on sex assigned at birth.
1. Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 7 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice:
* Refrain from donating fresh unwashed semen.
* Use contraception as follows as specified in the protocol
2. Female participants:
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a women of nonchildbearing potential OR
* Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of \< 1% per year), with low user dependency during the study intervention period and for at least 7 months after the last dose of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 3 days before the first dose of study intervention.
* Additional requirements for pregnancy testing during and after study intervention are provided in the protocol.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
15. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol.
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Has clinically confirmed leptomeningeal disease, in the opinion of the investigator.
2. Has uncontrolled or significant cardiovascular disease.
3. Has toxicity related to prior cancer therapy that has not resolved to ≤ Grade 1, with exceptions as stated in the protocol.
4. Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
5. Has an infection with HIV-1 or HIV-2, with the exception of participants with well-controlled HIV.
6. Has active hepatitis B or C infection.
7. Has an active SARS-CoV-2 infection. Participants with prior infection that has resolved per local institutions' requirements and screening guidance are eligible.
8. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab.
9. Is unable to receive trastuzumab treatment due to medical contraindications.
10. Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site.
11. Has any condition that would prevent treatment with the physician's choice of chemotherapy.
12. Has any issue or condition that in the opinion of the investigator would contraindicate the participant's participation in the study or confound the results of the study.
Prior/Concomitant Therapy
13. Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation.
14. The washout periods for prior anticancer therapies before randomization as specified in the protocol.
15. Has a history of trauma or major surgery within 4 weeks prior to randomization.
Other Exclusions
16. Has a known hypersensitivity to any components of the study drugs, including chemotherapy.
17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.

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Where can I participate?

CS Cancer Tarzana : Nikki Kem-Bernard
CS Cancer at Beverly Hills : Nikki Kem-Bernard
CS Cancer at Cedars-Sinai Medical Center : Nikki Kem-Bernard

More about this Clinical Trial

What is the full name of this clinical trial?

JZP598-303: A Phase 3, randomized, open-label, controlled study comparing the efficacy and safety of zanidatamab to trastuzumab, each in combination with physician s choice chemotherapy, for the treatment of participants with metastatic HER2-positive breast cancer

Study Details

Disease Type/Condition

Breast

Principal Investigator

Bitar, Jin Sun

Co-Investigators

Karissa Britten, Maryliza El-Masry, Mazen Jizzini, Natasha Banerjee, Ryan Ponec, Swati Sikaria, Syed Jilani, Thomas Lowe, Vanessa Dickey, Yuan Yuan

Age Group

Adult

Phase

III

IRB Number

STUDY00004548

ClinicalTrials.gov ID

NCT06435429

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Nikki Kem-Bernard

Email

[email protected]