Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors

Antje Wick, Oliver Bähr, Martin Schuler, Kristoffer Rohrberg, Sant P Chawla, Filip Janku, David Schiff, Volker Heinemann, Yoshitaka Narita, Heinz-Josef Lenz, Masafumi Ikeda, Yuichi Ando, Wolfgang Wick, Joachim P Steinbach, Michael C Burger, Katharina Wenger, Ulrik Lassen, Kamalesh K Sankhala, Cristiana Roggia, Isabelle GenvresseCatya Munhoz, Christine Rentzsch, Susanne Reschke, Simon Langer, Markus Wagner, Stefan Kaulfuss, Charles Cai, Eleni Lagkadinou, Michael Jeffers, Carol Peña, Ghazaleh Tabatabai


PURPOSE: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects.

PATIENTS AND METHODS: The study comprised of dose escalation and dose expansion cohorts. BAY1436032 tablets were orally administered twice daily on a continuous basis in subjects with mIDH1 solid tumors.

RESULTS: In dose escalation, 29 subjects with various tumor types were administered BAY1436032 across five doses (150-1,500 mg twice daily). BAY1432032 exhibited a relatively short half-life. Most evaluable subjects experienced target inhibition as indicated by a median maximal reduction of plasma R-2-hydroxyglutarate levels of 76%. BAY1436032 was well tolerated and an MTD was not identified. A dose of 1,500 mg twice daily was selected for dose expansion, where 52 subjects were treated in cohorts representing four different tumor types [lower grade glioma (LGG), glioblastoma, intrahepatic cholangiocarcinoma, and a basket cohort of other tumor types]. The best clinical outcomes were in subjects with LGG (n = 35), with an objective response rate of 11% (one complete response and three partial responses) and stable disease in 43%. As of August 2020, four of these subjects were in treatment for >2 years and still ongoing. Objective responses were observed only in LGG.

CONCLUSIONS: BAY1436032 was well tolerated and showed evidence of target inhibition and durable objective responses in a small subset of subjects with LGG.

Original languageEnglish
JournalClinical Cancer Research
Issue number10
Pages (from-to)2723-2733
Number of pages11
Publication statusPublished - 15 May 2021


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