A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients with Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected Malignancies

Exclusion Criteria

• •1. Participants who have received concurrent antitumor treatment or investigational products within 28 days or 5 half lives, whichever is shorter before the start of study intervention (e.g., chemotherapy, radiotherapy \[with the exception of palliative bone directed radiotherapy\], immunotherapy, targeted therapy, hormonal therapy, or cytokine therapy except for erythropoietin).
• •2. Participants who had major surgery within 28 days before the start of study intervention (excluding prior diagnostic biopsy).
• •3. Participants who had continuance of toxicities due to prior antitumor agents that have not resolved to Grade ≤ 1 per NCI CTCAE version 5.0, except alopecia, \< Grade 2 sensory neuropathy.
• •4. Participants with a history of immune mediated AE of any grade that resulted in discontinuation of prior immunotherapy.
• •5. Participants with previous malignant disease other than the target malignancy to be investigated in this study within the last 2 years with the exception of resected basal or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix or breast.
• •6. Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated and, at the time of screening, stable central nervous system (CNS) metastases are eligible, provided they meet all the following:
• •a. Brain imaging at screening shows no evidence of interim progression, participant is clinically stable for at least 2 weeks and without evidence of new brain metastases.
• •b. Measurable disease outside the CNS. c. No ongoing requirement for corticosteroids as therapy for CNS disease; off steroids 2 weeks before the first dose of AP203; anticonvulsants at a stable dose are allowed.
• •7. Participants who received any organ transplantation including allogeneic stem cell transplantation.
• •8. Participants with significant acute or chronic infections including, among others:
• •o Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• •Note: An HIV serology test (including antigen and/or antibodies) will be conducted at baseline for the participants with unknown HIV status and participants with positive HIV test will be excluded.
• •o Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV deoxyribonucleic acid (DNA) \> 500 IU/mL (or \> 2500 copies/mL) at screening.
• •Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA \< 500 IU/mL or \< 2500 copies/mL) can be enrolled. Participants with detectable HBsAg or detectable HBV DNA should be managed per treatment guidelines. Participants receiving antivirals at screening should have been treated for \> 2 weeks before the first dose of AP203.
• •o Participants with active hepatitis C. Note: Participants with a negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening are eligible. The HCV RNA test will be performed only for participants testing positive for HCV antibody. Participants receiving antivirals at screening should have been treated for \> 2 weeks before the first dose of AP203.
• •9. Participants with active or history of any autoimmune disease that may relapse (participants with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
• •10. Participants with known severe hypersensitivity reactions to monoclonal antibodies.
• •11. Participants with pregnancy or lactation period. (Note: a negative pregnancy test is required for WOCBP.)
• •12. Participants with known alcohol or drug abuse.
• •13. Participants with clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to the first dose of AP203), myocardial infarction (\< 6 months prior to the first dose of AP203), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
• •14. Participants with any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• •15. Participants with live vaccination within 28 days of the first dose of AP203 and while on study is prohibited.
• •16. Participants with all other significant diseases, in the opinion of the Investigator, might impair the participant's tolerance of the study intervention.
• •Dose expansion Phase specific Exclusion Criterion:
• •1. Participants who have received prior therapy with any PD-L1 x CD137 bispecific antibody.