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

Inclusion 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 (exceptBiliary Tract Cancer (BTC), defined as gallbladder cancer or cholangiocarcinoma) whohave progressed following at least 1 prior systemic treatment for metastatic oradvanced disease and have no available treatment options that have confirmedbenefit. Prior treatment with HER2-targeted therapy is not permitted (Cohort 1only). For participants with breast cancer (Cohort 2) or GEA (Cohort 3), priorHER2-targeted therapy is permitted and prior therapy with trastuzumab deruxtecan (T-DXd) is required.

3. HER2 overexpression (IHC 3+) must be determined by a sponsor designated centrallaboratory.

4. All participants must have adequate tumor sample for submission to allow centralHER2 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:

9. Participants also have measurable metastatic disease with HER2 overexpression (IHC 3+) outside the CNS.

10. Participants with treated CNS metastases that are no longer symptomatic may beincluded in the study if they recovered to < Grade 1 (CTCAE Version 5.0 orhigher) or baseline from the acute toxic effect associated with the treatment > 7 days prior to Cycle 1 Day 1.

11. Prior stereotactic radiosurgery or stereotactic radiotherapy should becompleted at least 7 days (≥ 7 days) before the first dose of studyintervention.

12. Adequate organ functions.

13. Females of childbearing potential must have a negative pregnancy test result.

14. Females of childbearing potential and males with a partner of childbearing potentialmust be willing to use 2 methods of birth control.

Exclusion Criteria:

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 SARS-CoV-2 infection.

8. Has a history of life-threatening hypersensitivity to monoclonal antibody (mAbs) orto recombinant proteins or excipients in the drug formulation of zanidatamab.

9. Has any serious underlying medical or psychiatric condition that would impair theability of the participant to receive or tolerate the planned treatment at theinvestigational site.

10. Has any issue or condition that, in the opinion of the investigator, wouldcontraindicate the participant's participation in the study or confound the resultsof 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 forbreast cancer, or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.

14. 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 andROS1 fusion.

17. Female participants who are breastfeeding or pregnant, and female and maleparticipants planning a pregnancy.

18. Prior or concurrent invasive malignancy other than the disease under study, whosenatural history or treatment has, in the opinion of the investigator or medicalmonitor, the potential to interfere with the safety or efficacy assessment of theinvestigational regimen.