Rodon, Jordi, Argiles, Guillem, Connolly, Roisin, Vaishampayan, Ulka, de Jonge, Maja, Garralda, Elena, Giannakis, Marios, Smith, David C., Dobson, Jason, McLaughlin, Margaret, Seroutou, Abdelkader, Ji, Yan, Morawiak, Jennifer, Moody, Susan and Janku, Filip (2021) Phase I study of single-agent WNT974 a first-in-class Porcupine inhibitor, in patients with advanced solid tumors. British journal of cancer : BJC, 125. pp. 28-37. ISSN 1532-1827

Abstract

This Phase I study assessed the safety and efficacy of the Porcupine inhibitor, WNT974, in patients with advanced solid tumors. Patients (n=94) received oral WNT974 at doses of 5–30 mg once daily (QD), plus additional dosing schedules. Maximum tolerated dose was not established; the recommended dose for expansion was 10 mg QD. Dysgeusia was the most common adverse event (50% of patients), likely resulting from on-target Wnt pathway inhibition. No responses were seen by RECIST v1.1 criteria; 16% of patients had stable disease (median duration 19.9 weeks). AXIN2 expression by RT-PCR was reduced in 94% of paired skin biopsies (n=52) and 74% of paired tumor biopsies (n=35), confirming inhibition of the Wnt pathway. In an exploratory analysis, an inverse association was observed between AXIN2 change and immune signature change in paired tumor samples (n=8), suggesting WNT974 may influence immune cell recruitment to tumors, and may enhance checkpoint inhibitor activity.

Item Type:	Article
Date Deposited:	10 Aug 2021 00:45
Last Modified:	10 Aug 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44492