Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors

Prior treatment

• Major surgical procedures within 28 days prior to enrolment.
• Treatment with any of the following anti-cancer therapies prior to the first dose of study drugs within the stated time frames:
  • Prior chemotherapy ≤ 2 weeks of C1 Day 1 of PRL3-ZUMAB.
  • Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks, whichever is shorter, prior to starting study drug.
  • Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks (whichever is shorter) prior to starting study drug.
  • Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug.
  • Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug.
• Prior stem cell or bone marrow transplant
• Vaccinated within 2 weeks from prior to the first administration of PRL3-ZUMAB

Other illness

• Known HIV infection.
• Patients requiring regular immunosuppressive medication for autoimmune disease or corticosteroid doses of \>10mg prednisolone for greater than 2 days
• History of another cancer within the last 2 years, with the exception of
  • Curatively resected non-melanomatous skin cancer,
  • Curatively treated cervical carcinoma in-situ,
  • Prostate cancer treated with leuteinizing hormone-releasing hormone (LH-RH) agonists/pure antagonists for at least 2 months

Other

• Untreated or symptomatic central nervous system metastases. Patients with treated brain metastases stable for 3 months are eligible to enroll.
• Pregnant or breast-feeding females.
• Unable to provide informed consent.

• Male or female patients 21 years of age or older at the time written informed consent is obtained.
• Histopathological- or cytological- documented advanced curatively unresectable solid tumors failing standard therapy.
  • For HCC must have failed at least 1 line of standard therapy.
  • For gastric cancer must have failed at least 2 line of standard therapy (inclusive of adjuvant treatment).
  • For other solid tumours must have failed at least 1 line of standard therapy.
• Progressive disease following the last treatment
• Life expectancy ≥ 4 months
• Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of ≤ 2 at study entry
• Recovery to Grade ≤ 1 by the Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE v 4.03), from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for cancer, with the exception of non-clinically significant adverse events such as alopecia; biochemical abnormalities, or resolved to Grade ≤ 2: peripheral neuropathy; hypertension and proteinuria.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test at study entry. Subjects not considered WOCBP are those without menses for 24 consecutive months, and those who have undergone hysterectomy and/or bilateral salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study.
• Adequate organ and hematological function as evidenced by the following laboratory studies within 10 days of 1st treatment:
  • Absolute neutrophil count ≥ 1.0 x 10\^9/L.
  • Platelet count ≥ 75 x 10\^9/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 ≤ 3 x ULN (≤ 5x ULN in the presence of liver mets).
  • For patients with hepatocellular carcinoma (HCC) Child Pugh score of ≤ B7.
  • Creatinine \< 1.5x ULN
• Evaluable or measurable disease by RECIST v1.1
• Patients with active Hepatitis B (defined as Hep B S Ag or DNA positive) need to be on anti-viral therapy while on PRL3-ZUMAB.