A First-in-Human Study of PRL3-ZUMAB

• Status: Unknown status
• Trial end date: 2020-02-20
• Target enrollment: 0
• Participant gender: All

Summary

This study is carried out to test the safety of a study drug called PRL3-ZUMAB. PRL3-ZUMAB is an investigational drug that has not yet been approved by the Food and Drug Administration (FDA) or any other regulatory authorities for commercial purposes. This is the first study in which PRL3-ZUMAB will be given to humans. The study drug has been tested in animals and was found to be well-tolerated with minimal side effects. This research study will test different doses of the drug to see which dose is safest in people.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Collaborator: INTRA-IMMUSG PRIVATE LIMITED

Criteria

Inclusion Criteria:

1. Signed informed consent. Written informed consent must be obtained prior to performing any study-related procedures.

2. Histopathological- or cytological- documented, measurable or non-measurable, locally advanced unresectable primary or metastatic solid tumor unresponsive to standard therapy or for which there is no standard therapy available.

3. Progressive disease (PD) during or following the last treatment regimen as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1 guidelines)

4. Haematologic malignancies study population for expansion cohort:

• Newly diagnosed early AML (age>65 years) who are unfit for the intensive chemotherapy and declined hypomethylating agent

• Elderly AML who failed first line of treatment including hypomethylating agent

• Relapsed or refractory AML who failed at least 1 line of salvage chemotherapy and are deemed unfit for further intensive chemotherapy

• Relapsed or refractory multiple myeloma who failed at least 3 lines of prior therapy and with measurable disease either by serum M-protein, involved immunoglobulin type or serum free light chain.

5. Life expectancy >3 months

6. Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of <= 2 at study entry

7. Age ≥ 21 years

8. Pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) ≥ 50%

9. 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 alopecia or peripheral neuropathy (the latter of which must have resolved to Grade ≤ 2).

10. 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.

11. Preserved organ function as defined below. All parameters must be evaluated within 7 days prior to the first dose of PRL3-ZUMAB:

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN), or ≤ 5.0 X ULN in subjects with metastatic liver disease

• Hemoglobin ≥ 9 g/dL

• Total bilirubin ≤ 1.5 × ULN

• Creatinine ≤ 1.5 × ULN

• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (only applicable to non-AML subject)

• Platelets ≥ 100 × 109/L (only applicable to non-AML subject)

Exclusion Criteria:

1. Prior anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, monoclonal antibodies, targeted therapy or investigational agents within 4 weeks (6 weeks for mitomycin C and nitrosoureas) prior to the first dose of PRL3-ZUMAB

2. Known symptomatic brain metastases. Subjects with treated brain metastasis (radiotherapy and/or surgery) will be eligible if they:

• Have completed treatment for their brain metastasis > 4 weeks prior to scheduled study treatment start date;

• Are neurologically stable;

• Are not receiving corticosteroids or corticosteroids in doses no greater than physiological replacement (e.g., dexamethasone < 1.5 mg/day); and

• Have a screening/baseline MRI scan of the brain that specifically verifies no evidence of CNS hemorrhage and no active gadolinium enhancing lesions.

3. Isolated CNS disease in AML cohort

4. Acute promyelocytic leukemia or AML M3

5. Non-secretary myeloma

6. Primary brain / CNS malignancy (e.g., gliomas, lymphomas)

7. Leptomeningeal disease

8. Pregnancy (confirmed by beta -human chorionicgonadotrophin [β-HCG] or lactating

9. Significant uncontrolled intercurrent illness including, but not limited to:

• ongoing or active infection requiring parenteral antibiotics; clinically significant cardiac disease [(class II, III, or IV of the New York Heart Association classification (NYHA)];

• unstable angina pectoris, myocardial infarction within 6 months or is post angioplasty or stenting within 6 months;

• uncontrolled hypertension (i.e., systolic blood pressure (BP) > 150 mm Hg, diastolic BP > 90 mm Hg), found on two consecutive measurements separated by a 1-week period;

• clinically significant cardiac arrhythmia; or

• uncontrolled diabetes.

10. Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

11. Known active hepatitis B or C or other active (nonmalignant) liver disease. Patients with hepatitis B surface antigen positive serology may participate if HBV DNA copy number is <100 copies/mL.

12. History of previously treated neurologic or other neurodegenerative diseases/disorders, or psychiatric illness, disability, or social situation that would compromise the subject's safety, ability to provide consent, or limit his/her compliance with study requirements

13. Prior hypersensitivity reaction to monoclonal antibodies or other therapeutic proteins, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-HT3 antagonists, or corticosteroids.

14. History of another primary cancer, with the exception of:

• curatively resected nonmelanomatous 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, or

• other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years.

15. Require treatment with prohibited concomitant medications

16. Prior stem cell or bone marrow transplant

17. Vaccinated within 8 weeks from prior to the first administration of PRL3-ZUMAB