Esophageal Cancer Clinical Trials

• Signed the informed consent form voluntarily and agreed to follow the program requirements

• Age: ≥18 years

• Has a life expectancy of ≥3 months

• Has documented locally advanced or metastatic solid tumor(s) that are known to potentially express CLDN18.2 as defined below that have recurred or progressed on at least 1 line of prior systemic therapy (including adjuvant/neoadjuvant), have no other standard of care options, and have no available curative options, including:

∙ Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (AC): Subjects with CLDN18.2, human epidermal growth factor receptor 2 (HER2), PD-L1 and/or microsatellite instability high (MSI-H)/ mismatch repair deficiency (dMMR) positive tumors must have received targeted treatment in their prior lines of therapy.

‣ Pancreatic ductal AC (PDAC): Subjects may enter screening prior to completing the first line of standard therapy.

‣ Esophageal AC (EAC): Subjects with HER2, PD-L1 and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.

‣ Biliary tract cancers (BTCs): Subjects with HER2 overexpression, NTRK fusions, KRAS mutations, IDH1 mutations, FGFR2 fusions, BRAF mutations and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.

‣ Other solid tumors not specified above may be included IF they have documented CLDN18.2 expression by IHC (1+). As applicable per standard of care, subjects with HER2 and/or PD-L1 positive tumors must have received targeted treatment in their prior lines of therapy, and subjects with MSI-H or dMMR positive tumors must have received immune checkpoint inhibitor.

• Agree to provide most recent existing tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or slides) from primary or metastatic sites (see details in Section 7.1.1) for tissue-based evaluation of CLDN18.2 expression. A fresh biopsy is required if no archival/FFPE block or slides are available. Re-biopsy is recommended if the subject previously received a CLDN18.2-directed treatment.

• Has at least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) v1.1

• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1

• Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by the National Cancer Institute (NCI) CTCAE v5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2

• Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%

⁃ Has adequate organ function before enrollment, defined as:

• Marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, platelet count (PLT) ≥100×109/L, hemoglobin (Hb) ≥9.0 g/dL (blood transfusion, platelet transfusion, erythropoietin, hematopoiesis agents, and granulocyte-colony stimulating factor \[G-CSF\] use are not allowed 1 week prior to screening)

∙ Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) (≤3×ULN for subjects with Gilbert's syndrome or liver metastasis at baseline), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) without liver metastasis ≤3.0×ULN, AST and ALT with liver metastasis ≤5.0×ULN NOTE: For patients with Gilbert's syndrome, conjugated bilirubin ≤1.5×ULN and TBIL \<3.0×ULN in the absence of liver metastases.

∙ Renal function: Creatinine (Cr) clearance ≥60 mL/min (Cockcroft-Gault equation) or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation)

⁃ Coagulation parameters: International normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, unless receiving anticoagulation therapy with prothrombin time and aPTT levels within the intended therapeutic range

⁃ Urine protein ≤2+ or ≤1000 mg/24 hours

⁃ Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix E) during the course of the study and after the last dose of study treatment (7 months for women and 4 months for men). An additional contraceptive method, such as a barrier method (eg, condom), is recommended.

⁃ Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female subjects are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes. In addition, females \<55 years old must have a serum follicle stimulating hormone (FSH) level \>40 mIU/mL to confirm menopause.

⁃ Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.