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A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies.
Chee, Cheng E; Ooi, Melissa; Lee, Soo-Chin; Sundar, Raghav; Heong, Valerie; Yong, Wei-Peng; Ng, Chin Hin; Wong, Andrea; Lim, Joline S J; Tan, David S P; Soo, Ross; Tan, Joshua T C; Yang, Song; Thura, Min; Al-Aidaroos, Abdul Qader; Chng, Wee Joo; Zeng, Qi; Goh, Boon-Cher.
Afiliação
  • Chee CE; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore. mdccce@nus.edu.sg.
  • Ooi M; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. mdccce@nus.edu.sg.
  • Lee SC; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Sundar R; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Heong V; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Yong WP; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Ng CH; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Wong A; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Lim JSJ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Tan DSP; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Soo R; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Tan JTC; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Yang S; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Thura M; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Al-Aidaroos AQ; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Chng WJ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Zeng Q; Department of Hematology-Oncology, National University Cancer Institute, Singapore (NCIS), 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, 119228, Singapore.
  • Goh BC; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Target Oncol ; 18(3): 391-402, 2023 05.
Article em En | MEDLINE | ID: mdl-37060431
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Neoplasias Hematológicas / Neoplasias / Antineoplásicos Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: Target Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Singapura

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Neoplasias Hematológicas / Neoplasias / Antineoplásicos Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: Target Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Singapura