A First-in-Human Study of PRL3-ZUMAB

NCT03191682 | Active Not Recruiting Phase 1

• 1 other identifier: MC03/06/16
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Incidence of Grade 3 or 4 drug related adverse events and clinical lab abnormalities defined as Dose Limiting Toxicities (DLTs) using NCI CTCAE v 4.03

  During cycle 1 (28 days) of treatment

• Maximum tolerated dose of PRL3-zumab, defined as the highest dose level at which < 33% of 6 patients experience a dose-limiting toxicity graded according to Common Terminology Criteria for Adverse Events version 4 (Phase I)

  28 days

• Recommended Phase 2 Dose (RP2D) of PRL3-zumab defined as the most appropriate dose to maximize a favorable risk/benefit reward for the participant population

  After completion of all Cycle 1 (28 days) of treatment for participant enrolled in part 1

Secondary Outcomes (1)

• Total Active Pharmaceutical Ingredient (API) levels in plasma

  The pharmacokinetics profile will be assessed by blood collection during Cycle 1 (28 days) of treatment

Study Arms (1)

PRL3-ZUMAB

EXPERIMENTAL

The starting dose will be 0.3 mg/kg, administered Q2 weekly, with the subsequent dose levels being 0.9 mg/kg, 3.0 mg/kg, and 6.0 mg/kg, all administered on a Q2 weekly basis until disease progression

Drug: PRL3-ZUMAB

Interventions

PRL3-ZUMAB DRUG

The starting dose will be 0.3 mg/kg, administered Q2 weekly, with the subsequent dose levels being 0.9 mg/kg, 3.0 mg/kg, and 6.0 mg/kg, all administered on a Q2 weekly basis until disease progression. The investigator will monitor each subject for the occurrence of AEs. In event of infusion-related adverse events, the Investigator, in consultation with the PI, may increase the duration of the infusion over a period of up to 24 hours at their discretion. Dosing will continue in a standard 3+3 design for dose escalation.

PRL3-ZUMAB

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent. Written informed consent must be obtained prior to performing any study-related procedures.
• 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.
• 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)
• 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.
• Life expectancy \>3 months
• Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of \<= 2 at study entry
• Age ≥ 21 years
• Pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) ≥ 50%
• 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).
• 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.
• Preserved organ function as defined below. All parameters must be evaluated within 7 days prior to the first dose of PRL3-ZUMAB:

You may not qualify if:

• 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
• 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.
• Isolated CNS disease in AML cohort
• Acute promyelocytic leukemia or AML M3
• Non-secretary myeloma
• Primary brain / CNS malignancy (e.g., gliomas, lymphomas)
• Leptomeningeal disease
• Pregnancy (confirmed by beta -human chorionicgonadotrophin \[β-HCG\] or lactating
• 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;

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• INTRA-IMMUSG PRIVATE LIMITED: collaborator

Study Sites (1)

National University Hospital

Singapore, Singapore, 119.074, Singapore

Location

Related Publications (4)

• Zeng Q, Hong W, Tan YH. Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1. Biochem Biophys Res Commun. 1998 Mar 17;244(2):421-7. doi: 10.1006/bbrc.1998.8291.

  PMID: 9514946 BACKGROUND

• Al-Aidaroos AQ, Zeng Q. PRL-3 phosphatase and cancer metastasis. J Cell Biochem. 2010 Dec 1;111(5):1087-98. doi: 10.1002/jcb.22913.

  PMID: 21053359 BACKGROUND

• Walls CD, Iliuk A, Bai Y, Wang M, Tao WA, Zhang ZY. Phosphatase of regenerating liver 3 (PRL3) provokes a tyrosine phosphoproteome to drive prometastatic signal transduction. Mol Cell Proteomics. 2013 Dec;12(12):3759-77. doi: 10.1074/mcp.M113.028886. Epub 2013 Sep 12.

  PMID: 24030100 BACKGROUND

• Chee CE, Ooi M, Lee SC, Sundar R, Heong V, Yong WP, Ng CH, Wong A, Lim JSJ, Tan DSP, Soo R, Tan JTC, Yang S, Thura M, Al-Aidaroos AQ, Chng WJ, Zeng Q, Goh BC. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Target Oncol. 2023 May;18(3):391-402. doi: 10.1007/s11523-023-00962-w. Epub 2023 Apr 15.

  PMID: 37060431 DERIVED

Study Officials

• Cheng Ean Chee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2017
• First Posted: June 19, 2017
• Study Start: February 20, 2017
• Primary Completion (Estimated): February 20, 2027
• Study Completion (Estimated): February 20, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)