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

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

Cell Reports Medicine

10.1016/j.xcrm.2025.102120

https://doi.org/10.1016/j.xcrm.2025.102120

David J. Park, Min Thura, Vi K. Chiu, Brian Vicuna, Koon Hwee Ang, Blanca Sanchez, Pei Ling Chia, Kam Yew Kuan, Jie Li, Ke Zhang, Wei Hui Zheng, Matthew Chau Hsien Ng, Qi Zeng

General Medicine

20 May 2025

Park, D. J., Thura, M., Chiu, V. K., Vicuna, B., Ang, K. H., Sanchez, B., Chia, P. L., Kuan, K. Y., Li, J., Zhang, K., Zheng, W. H., Hsien Ng, M. C., & Zeng, Q. (2025). The PRL3-zumab paradigm: A multicenter, single-dose-level phase 2 basket clinical trial design of an unconventional cancer immunotherapy. Cell Reports Medicine, 6(5), 102120. https://doi.org/10.1016/j.xcrm.2025.102120

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-in-class 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 clinical benefits in late-stage IV solid cancer patients. This trial is registered at ClinicalTrials.gov as NCT04452955.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This study was funded by Intra-ImmuSG Pte Ltd, an A∗STAR (Agency for Science, Technology and Research, Singapore) spin-off company. IMCB core fund was used for publication fee.

Cell Reports Medicine 6, 102120, May 20, 2025 © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

https://oar.a-star.edu.sg/communities-collections/articles/22883

2666-3791

Institute of Molecular and Cell Biology