A Study of Zanidatamab (ZW25) With Evorpacept (ALX148) in Patients With Advanced HER2-expressing Cancer

Inclusion Criteria:

• Locally advanced (inoperable) and/or metastatic HER2-expressing cancer based onlocal or central laboratory test results as follows:

• Parts 1 and 2: HER2-positive breast cancer as defined per American Society ofClinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines

• Parts 1 and 2: HER2-low breast cancer (defined as immunohistochemistry [IHC] 1+or IHC 2+; AND is currently not and has never been HER2-positive per theASCO/CAP guidelines)

• Part 2: HER2-positive gastroesophageal adenocarcinoma as defined per theASCO/CAP gastric cancer-specific guidelines; or other HER2-overexpressingnon-breast cancers (defined as IHC 3+; or IHC 2+ and in situ hybridization [ISH]+) per the ASCO/CAP guidelines for breast cancer

• Progression after or during the most recent systemic regimen of treatment foradvanced cancer. For both Part 1 and Part 2, prior therapies must have includedapproved agents known to confer clinical benefit.

• Subjects with HER2-positive breast cancer who did not receive trastuzumab orpertuzumab due to medical contraindications will not be eligible for this study

• Subjects with HER2-low breast cancer who have received prior HER2-targetedtherapy (other than trastuzumab deruxtecan, which is allowed but not required)will not be eligible for this study

• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

• Willingness to undergo a new biopsy to provide a tumor tissue for central laboratorytesting of HER2 protein expression and gene amplification by IHC and ISH assays,respectively

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate organ functions

• Adequate cardiac left ventricular function, as defined by a left ventricularejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiplegated acquisition scan (MUGA) obtained within 4 weeks prior to first dose of studytreatment

Exclusion Criteria:

• Previous allogeneic stem cell transplant

• Prior treatment with any anti-CD47 or anti-signal regulatory protein alpha (SIRPα)agent

• Prior or concurrent invasive malignancy whose natural history or treatment has, inthe opinion of the investigator or medical monitor, the potential to interfere withthe safety or efficacy assessment of the investigational regimen

• Received systemic anticancer therapy within 4 weeks of starting study treatment (6weeks for mitomycin C or nitrosoureas). Received radiotherapy within 2 weeks of thefirst dose of zanidatamab/evorpacept (ALX148)

• Untreated brain metastases, symptomatic brain metastases; or radiation treatment (stereotactic radiosurgery and whole brain radiation) for brain metastases within 2weeks of start of study treatment

• Known leptomeningeal disease

• Active hepatitis

• Infection with human immunodeficiency virus (HIV)-1 or HIV-2. (Exception: Subjectswith well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] areeligible.)

• QTc Fridericia (QTcF) > 470 ms

• History of myocardial infarction or unstable angina within 6 months prior toenrollment, troponin levels consistent with myocardial infarction, or clinicallysignificant cardiac disease, such as ventricular arrhythmia requiring therapy,uncontrolled hypertension, or any history of symptomatic congestive heart failure

• Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease