The PRL3-zumab paradigm: A multicenter, single-dose-level phase 2 basket clinical trial design of an unconventional cancer immunotherapy.
Publication Title
Cell Rep Med
Document Type
Article
Publication Date
5-20-2025
Keywords
Humans; Neoplasms; Immunotherapy; Antibodies, Monoclonal, Humanized; Female; Male; Protein Tyrosine Phosphatases; Middle Aged; Neoplasm Proteins; Aged; Adult; EES set; FAS set; PFS; PRL3; PRL3-zumab; SEPSC; efficacy evaluable set,; full analysis set,; historical data; intra-patient comparison; intracellular oncoprotein; phase 2 basket clinical trial; single evaluable patient single cohort,; california; fullerton; st jude
Abstract
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.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
DOI
10.1016/j.xcrm.2025.102120
