An Open Label Phase II Study of the Efficacy and Tolerability of PRL3-ZUMAB and Predictive Biomarkers in Advanced Solid Tumours
This is a Phase II, open-label, single dose level study of PRL3-ZUMAB monotherapy in patients with advanced solid tumours that have failed standard therapy. Approximately 30 patients will be recruited with \ 10 gastric cancers and \ 10 hepatocellular carcinomas. Patients who have received at least 1 dose of PRL3-ZUMAB will be evaluable for toxicity and efficacy. PRL3-ZUMAB will be given IV every 2 weeks for up to 12 infusions in the absence of unmanageable toxicities or disease progression. Patients who are benefitting from the treatment may continue on PRL3-ZUMAB beyond 12 infusions with the agreement of the study drug provider. PRL3-ZUMAB at the RP2D in tumour types enriched for known PRL-3 expression for efficacy and tolerability will be evaluated. There will also be in depth molecular profiling of tissues in patients who have an objective response or prolonged disease stabilization to identify predictive/selection biomarkers as well as evaluation of the oncogenic signaling modulation and immunomodulation by PRL3-ZUMAB and its potential for future combination with other targeted therapies or immunotherapy.
• 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.