ATX-101, a cell-penetrating protein targeting PCNA, can be safely administered as intravenous infusion in patients and shows clinical activity in a Phase 1 study

Charlotte Rose Lemech, Ganessan Kichenadasse, Jens-Peter Marschner, Konstantinos Alevizopoulos, Marit Otterlei, Michael Millward

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Proliferating Cell Nuclear Antigen (PCNA) is a highly conserved protein essential for DNA replication, repair and scaffold functions in the cytosol. Specific inhibition of PCNA in cancer cells is an attractive anti-cancer strategy. ATX-101 is a first-in-class drug targeting PCNA, primarily in cellular stress regulation. Multiple in vivo and in vitro investigations demonstrated anti-cancer activity of ATX-101 in many tumor types and a potentiating effect on the activity of anti-cancer therapies. Healthy cells were less affected. Based on preclinical data, a clinical phase 1 study was initiated. Twenty-five patients with progressive, late-stage solid tumors were treated with weekly ATX-101 infusions at four dose levels (20, 30, 45, 60 mg/m(2)). ATX-101 showed a favorable safety profile supporting that vital cellular functions are not compromised in healthy cells. Mild and moderate infusion-related reactions were observed in 64% of patients. ATX-101 was quickly cleared from blood with elimination half-lives of less than 30 min at all dose levels, probably due to both, a quick cell penetration and peptide digestion in serum, as demonstrated in vivo. No tumor responses were observed but stable disease was seen in 70% of the efficacy population (n = 20). Further studies have been initiated to provide evidence of efficacy.

Original languageEnglish
Number of pages4
JournalOncogene
DOIs
Publication statusE-pub ahead of print - 23 Dec 2022

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