The PRL3-zumab paradigm - A multicenter - single-dose-level phase 2 basket clinical trial design - of an unconventional cancer immunotherapy

Sep 23, 2026

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FDA-approved phase 2 basket trial design for PRL3-zumab in advanced solid tumors, focusing on safety and efficacy assessment across heterogeneous cancers. PRL3 is described as an intracellular oncotarget highly expressed across multiple cancers, while PRL3-zumab is presented as a first-in-class humanized IgG1 antibody with high affinity to PRL3. A full analysis set supports pharmacokinetic and safety analyses, and efficacy is evaluated using a single evaluable patient single cohort approach with stringent historical and within-patient controls, yielding longer PFS versus prior anti-PD-(L)1 lines.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

In brief

Summary

Introduction

Antibody-based targeting and intracellular PRL3

Article The PRL3-zumab paradigm: A multicenter, singledose-level phase 2 basket clinical trial design of an unconventional cancer immunotherapy Authors David J. Park, Min Thura, Vi K. Chiu, , Wei Hui Zheng, Matthew Chau Hsien Ng, Qi Zeng Correspondence [mthura@imcb.a-star.edu.sg](mthura@imcb.a-star.edu.sg) (M.T.), [mcbzengq@imcb.a-star.edu.sg](mcbzengq@imcb.a-star.edu.sg) (Q.Z.) In brief [Park et al. report](Park et al. report) the results of a FDAapproved phase 2 basket trial in advanced solid tumors for PRL3-zumab, a humanized antibody drug for cancer immunotherapy. PRL3-zumab shows its excellent drug safety and provides longer progression-free survival than historical data and prior lines of anti-PD-(L)1 therapies. • PRL3-zumab, a humanized antibody, binds to externalized PRL3 for cancer immunotherapy • PRL3-zumab demonstrates its excellent safety: no drugrelated >grade 2 adverse events • PRL3-zumab shows its efficacies by providing longer PFS compared to historical data Park et al., 2025, Cell Reports Medicine 6, 102120 May 20, 2025 © 2025 The Author(s) . Published by Elsevier Inc. [https://doi.org/10.1016/j.xcrm.2025.102120](https://doi.org/10.1016/j.xcrm.2025.102120) ll ll OPEN ACCESS Article The PRL3-zumab paradigm: A multicenter, single-dose-level phase 2 basket clinical trial design of an unconventional cancer immunotherapy David J. Park,1,11 Min Thura,2,11,* Vi K. Chiu,3 Brian Vicuna,4 Koon Hwee Ang,2 Blanca Sanchez,1 Pei Ling Chia,2 Kam Yew Kuan,2 Jie Li,2 Ke Zhang,2,5 Wei Hui Zheng,2,6 Matthew Chau Hsien Ng,7,9 and Qi Zeng2,8,10,12,* 1St Jude Crosson Cancer Institute/ Providence Medical Foundation, St. Jude Heritage Medical Group, Fullerton, CA, USA 2Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), 61 boipolis drive, Singapore 138673, Singapore 3The Angeles Clinic & Research Institute, a Cedars-Sinai affiliate, Santa Monica, CA, USA 4Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, USA 5Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China 6Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Hangzhou, Zhejiang, China 7Department of GI Oncology, National Cancer Centre Singapore, Singapore, Singapore 8The Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore 9Duke-NUS School of Medicine, Singapore, Singapore 10The INTRA-IMMUSG PTE LTD, Singapore, Singapore 11These authors contributed equally 12Lead contact *[Correspondence:](Correspondence: mthura@imcb.a-star.edu.sg)[ mthura@imcb.a-star.edu.sg](Correspondence: mthura@imcb.a-star.edu.sg) (M.T.), [mcbzengq@imcb.a-star.edu.sg](mcbzengq@imcb.a-star.edu.sg) (Q.Z.) [https://doi.org/10.1016/j.xcrm.2025.102120](https://doi.org/10.1016/j.xcrm.2025.102120) SUMMARY This Food and Drug Administration (FDA)-approved phase 2 basket trial has three highlights: (1) PRL3, an intracellular oncotarget that is highly (∼80.6%) expressed in multiple cancers; (2) PRL3-zumab, the first-inclass humanized antibody (immunoglobulin G1 [IgG1]) with high affinity to PRL3 (Kd = 7.57 pM); and (3) proof of concept: targeting intracellular oncoprotein with antibody-based therapy. A full analysis set (FAS, 51 patients received ≥1 dose) is used for pharmacokinetic and safety studies. Out of FAS, 20 patients are eligible to constitute the efficacy evaluable set (EES) . To circumvent the heterogeneities from different individuals/cancers, we propose single evaluable patient single cohort (SEPSC) and apply comparison using double stringent/rigorous controls with (1) historical progression-free survival (PFS) and (2) prior lines’ PFS within the same patients. PRL3-zumab shows longer PFS than prior line(s) of anti-PD-(L)1 therapies. PRL3-zumab demonstrates excellent safety and clear clin

FAQs

What is the core purpose of the PRL3-zumab phase 2 basket trial design?

To evaluate PRL3-zumab for advanced solid tumors, emphasizing safety and efficacy measured by progression-free survival across multiple cancer types under a basket-trial framework.

How does the study define safety and pharmacokinetic evaluation compared with efficacy?

A full analysis set (51 patients receiving at least one dose) is used for pharmacokinetic and safety studies, while an efficacy-evaluable set consisting of 20 eligible patients is used for efficacy evaluation.

Why does the design use historical PFS and prior-line PFS controls?

To address heterogeneity across individuals and cancers, the trial compares outcomes using stringent controls derived from historical progression-free survival and prior-line PFS within the same patients.

Sep 23, 2026

Uploaded by Fahsai