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Phase I study of single-agent WNT974 a first-in-class Porcupine inhibitor, in patients with advanced solid tumors

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

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