Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 May;18(3):391-402.
doi: 10.1007/s11523-023-00962-w. Epub 2023 Apr 15.

A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies

Cheng E Chee  1   2 , Melissa Ooi  3   4 , Soo-Chin Lee  3   4   5 , Raghav Sundar  3   4 , Valerie Heong  3 , Wei-Peng Yong  3   5 , Chin Hin Ng  3 , Andrea Wong  3 , Joline S J Lim  3   4 , David S P Tan  3   4   5 , Ross Soo  3 , Joshua T C Tan  3 , Song Yang  3 , Min Thura  6 , Abdul Qader Al-Aidaroos  6 , Wee Joo Chng  3   4   5 , Qi Zeng  6 , Boon-Cher Goh  3   5
Affiliations
Clinical Trial

A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies

Cheng E Chee et al. Target Oncol. 2023 May.

Abstract

Background: Phosphatase of regenerating liver-3 (PRL-3) is involved in cellular processes driving metastasis, cell proliferation, invasion, motility and survival. It has been shown to be upregulated and overexpressed in cancer tissue, in contrast to low or no expression in most normal tissue. PRL3-zumab is a first-in-class humanized antibody that specifically binds to PRL-3 oncotarget with high affinity and has been shown to reduce tumor growth and increase survival.

Objective: In the study, we aimed to determine the safety and efficacy of PRL3-zumab in patients with advanced solid tumors and hematological malignancies.

Methods: We conducted a phase I, first-in-human study in advanced solid tumors and hematological malignancies to investigate the safety, tolerability and efficacy of PRL3-zumab. Response rates were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) for solid tumors. For acute myeloid leukemia (AML) patients, bone marrow response criteria based on the European Leukaemia Network (ELN) 2017 guidelines for AML were used. We also explored the pharmacokinetics and pharmacodynamic relationships of PRL3-zumab in patients. This study was registered with ClinicalTrials.gov: NCT03191682.

Results: In the dose-escalation cohort, 11 patients with advanced solid tumors were enrolled into the study. An additional 12 patients with solid tumors and four patients with AML were enrolled in the dose-expansion cohort. Maximum tolerability was not achieved in this study, as there were no dose-limiting toxicities. Potential treatment-emergent adverse events were grade 1 increased stoma output and fatigue and grade 2 vomiting. Best response observed was stable disease in three solid-tumor patients (11.1%). The pharmacokinetics of PRL3-zumab were dose proportional, consistent with an IgG type monoclonal antibody.

Conclusions: PRL3-zumab, a first-in-class humanized antibody, was safe and tolerable in solid tumors and hematological malignancies.

PubMed Disclaimer

Conflict of interest statement

Qi Zeng is the founder of Intra-ImmuSG Pte. Ltd (IISG), an A*STAR spin-off company that provided PRL3-zumab for this study. Cheng E. Chee, Melissa Ooi, Soo-Chin Lee, Raghav Sundar, Valerie Heong, Wei-Peng Yong, Chin Hin Ng, Andrea Wong, Joline SJ Lim, David SP Tan, Ross Soo, Joshua TC Tan, Song Yang, Min Thura, Abdul Qader Al-Aidaroos, Wee Joo Chng and Boon-Cher Goh declare that they have no conflicts of interest that might be relevant to the contents of this article.

Figures

Fig. 1
Fig. 1
Flow diagram of study participants
Fig. 2
Fig. 2
Mean concentration–time curves of PRL3-zumab, stratified by dose levels in the dose-escalation cohort. Each plot represents the average serum concentration of patients in the dose-level group at a particular time point (mean ± SD): N = 3 (0.3 mg/kg); N = 2 (0.9 mg/kg); N = 3 (3 mg/kg); N = 3 (6 mg/kg). SD standard deviation
Fig. 3
Fig. 3
Mean concentration–time curves of PRL3-zumab (6 mg/kg) in the dose-expansion cohort. Each plot represents the average serum concentration of patients at a particular time point (mean ± SD): N = 12 (solid tumor); N = 4 (hematological malignancy). SD standard deviation
See this image and copyright information in PMC

References

    1. 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;244(2):421–427. doi: 10.1006/bbrc.1998.8291. - DOI - PubMed
    1. Zeng Q, Si X, Horstmann H, Xu Y, Hong W, Pallen CJ. Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome. J Biol Chem. 2000;275(28):21444–21452. doi: 10.1074/jbc.M000453200. - DOI - PubMed
    1. Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, et al. A phosphatase associated with metastasis of colorectal cancer. Science. 2002;294:1343–1346. doi: 10.1126/science.1065817. - DOI - PubMed
    1. Al-Aidaroos AQ, Zeng Q. PRL-3 phosphatase and cancer metastasis. J Cell Biochem. 2010;111(5):1087–1098. doi: 10.1002/jcb.22913. - DOI - PubMed
    1. Thura M, Al-Aidaroos AQO, Yong WP, Kono K, Gupta A, Lin YB, et al. PRL3-zumab, a first-in-class humanized antibody for cancer therapy. JCI Insight. 2016;1(9):e87607. doi: 10.1172/jci.insight.87607. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

Associated data