A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors

Eligibility Criteria

• 1. Is at least 18 years of age inclusive at the time of signing the informed consent
• 2. Participants with locally advanced, unresectable, or metastatic solid tumors (except Biliary Tract Cancer (BTC), defined as gallbladder cancer or cholangiocarcinoma) who have progressed following at least 1 prior systemic treatment for metastatic or advanced disease and have no available treatment options that have confirmed benefit. Prior treatment with HER2-targeted therapy is not permitted (Cohort 1 only). For participants with breast cancer (Cohort 2) or GEA (Cohort 3), prior HER2-targeted therapy is permitted and prior therapy with trastuzumab deruxtecan (T-DXd) is required.
• 3. HER2 overexpression (IHC 3+) via Immunohistochemistry (IHC).
• 4. All participants must have adequate tumor sample for submission to allow central HER2 testing.
• 5. Presence of at least 1 measurable lesion as assessed by Independent Central Review (ICR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• 6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 7. Has a life expectancy of at least 3 months, in the opinion of the investigator.
• 8. Participants with history of treated and stable CNS metastases are eligible, provided the following criteria are met:
• 1. Participants also have measurable metastatic disease with HER2 overexpression (IHC 3+) outside the CNS.
• 2. Prior stereotactic radiosurgery or stereotactic radiotherapy should be completed at least 7 days (≥ 7 days) before the first dose of study intervention.
• 3. Recovery to no more than Grade 1 or baseline from any acute toxicity associated with the treatment.
• 9. Adequate organ functions.
• 10. Females of childbearing potential must have a negative pregnancy test result.
• 11. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.
• 1. Has known or suspected leptomeningeal disease and/or untreated brain metastasis.
• 2. Has uncontrolled or significant cardiovascular disease
• 3. Has ongoing toxicity related to prior cancer therapy
• 4. Has uncontrolled infection or requiring IV antibiotics, antivirals, or antifungals.
• 5. Has known Human Immunodeficiency Virus (HIV) infection.
• 6. Has active hepatitis B or C infection.
• 7. Has an active severe acute respiratory syndrome coronavirus 2 infection.
• 8. Has a history of life-threatening hypersensitivity to monoclonal antibody (mAbs) or to recombinant proteins or excipients in the drug formulation of zanidatamab.
• 9. 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.
• 10. 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.
• 11. Prior treatment with HER2-targeted therapy (Cohort 1 only).
• 12. Has a history of trauma or major surgery
• 13. Was treated with systemic antineoplastic therapy, including hormonal therapies for breast cancer, or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to enrollment.
• 14. Was treated in a prior clinical study of zanidatamab or received zanidatamab at any time prior to the current study.
• 15. Colorectal Cancer (CRC) participants with known KRAS/NRAS and BRAF mutations.
• 16. Non-Small Cell Lung Cancer (NSCLC) participants with known ALK, EGFR mutations and ROS1 fusion.
• 17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.