PRL3-Zumab in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Men and women aged 18 or older with unresectable or metastatic solid tumors
2. Patients with locally advanced or metastatic solid tumors who have failed standard therapy or for whom no standard therapy is available. Treatment failure is defined as disease progression during or after systemic antitumor therapy (including but not limited to chemotherapy, radiotherapy, biologic therapy, immunotherapy, and endocrine therapy), or intolerance to treatment-related toxicities. Disease progression must be documented by radiographic evidence or clinical evidence. For patients who have received adjuvant or neoadjuvant therapy (radiotherapy or chemoradiotherapy), disease progression occurring during treatment or after completion of such therapy will be considered treatment failure.
3. Willing to provide written informed consent for the study.
4. Histopathological diagnosis and metastatic status cancer at study entry.
5. Must have received no more than 3 prior lines of treatment for metastatic disease.
6. Life expectancy of more than 6 months
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
8. Patient should have recovered from toxicity of prior treatment regimen to Grade 1 level except for alopecia or peripheral neuropathy or fatigue as defined by Common Terminology Criteria for Adverse Events (CTCAE version 5.
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at study entry and must follow highly effective contraception

   1. WOCBP must be willing to use highly effective methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide,) for the duration of the study and 90 days thereafter.
   2. Male participants should take precaution to avoid pregnancy in sexual partner during the study and 90 days thereafter.
10. Adequate organ and hematological function as evidenced by the following laboratory studies within 10 days of treatment:

    * Absolute neutrophil count ≥ 1.0 x 109/L to 8.0 × 10⁹/L.
    * Lymphocyte count ≥ 0.9 × 10⁹/L
    * Platelet count ≥ 75 x 109/L.
    * Hemoglobin ≥ 9 g/dL.
    * Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
    * Total bilirubin ≤ 1.5x ULN.
    * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN in the presence of liver metastases).
    * For patients with hepatocellular carcinoma (HCC) Child Pugh score of ≤ B7.
    * Creatinine \< 1.5x ULN. Creatinine clearance (according to Cockcroft-Gault Equation or by 24-hour urine collection) of \> 60 mL/min at study entry.
11. According to RECIST 1.1 and iRECIST, patients mush have at least one measurable lesion that meets the following criteria: Accurately measureable at baseline. Longest diameter ≥10mm at baseline (for lymph nodes, short axis ≥ 15mm). Measurable by a reproducible imaging method such as computed tomography (CT) or magnetic resonance imaging (MRI). If only one measurable lesion is present, it must not have been previously treated with local therapy such as radiotherapy.

Exclusion Criteria:

1. Patient has known untreated or symptomatic central nervous system metastasis.
2. Female patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 150 days (for pregnancy or conception) or 30 days (for breastfeeding) after the last dose of study treatment.
3. Patient with any of the following virologic findings:

   * Positive hepatitis B surface antigen (HBsAg) and positive HBV DNA
   * Positive anti-HIV antibody and positive HCV RNA
   * Positive HIV antibody
4. Patients with active autoimmune disease requiring systemic treatment, or with a history of autoimmune disease that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis), or patients at high risk (e.g., prior organ transplantation requiring immunosuppressive therapy).
5. Patient is receiving systemic glucocorticoids (only if higher than 10 mg or equivalent of prednisolone daily) or other immunosuppressive treatment for autoimmune disease or any other medical condition.
6. Patient has experienced a severe hypersensitivity reaction to another monoclonal antibody.
7. Patient has received treatment with any systemic anti-cancer therapies within 3 weeks prior to starting study treatment.
8. Patient has undergone radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study treatment.
9. Patient has received \> 3 lines of prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant chemotherapy treatment completed at least 1-year prior is not to be included in this).
10. Patient is unable to provide informed consent.
11. Patient has a history of another active cancer (which requires treatment and not considered cured by the investigator) within the last 2 years.
12. Patient has received a prior stem cell or bone marrow transplant.
13. Patient has received a live vaccine within 12 weeks of the first dose of PRL3-zumab. (Seasonal influenza vaccines that do not contain live virus are permitted).
14. Patient is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks prior to the anticipated first dose of study treatment in this study.
15. Patients with spinal cord compression caused by tumor, unless the condition has been treated and clinically stable for more than 1 month.
16. Patients with any unstable medical condition or any other disease that may compromise their safety or compliance with the study, including any severe or uncontrolled systemic disease such as uncontrolled hypertension, uncontrolled diabetes mellitus, or active bleeding.
17. Patients with alcohol dependence or a history of drug abuse or substance abuse within 1 year prior to study entry.
18. Patients with any other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality, that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results.
19. Patients who, in the investigator's judgment, are not suitable for participation in this study.