BAY1436032

P1, N=81, Active, not recruiting, Bayer | Trial completion date: Dec 2023 --> Dec 2024

In two clinical trials (N=192) on ND mIDH-2 AML patients, ORR was 74%-89%, CR was 54%-55%, and MLFS was 4%-11% with enasidenib + chemotherapy/azacytidine as compared to ORR of 36%, CR of 12%, and MLFS of 0% with azacytidine alone...In two clinical trials, ORR with BAY1436032 (N=27) and olutasidenib (N=123) were 15% and 46% respectively...Olutasidenib was also effective in patients with R/R mIDH-1 AML. More randomized double-blind multicenter clinical trials are needed to confirm these results.

P1, N=81, Active, not recruiting, Bayer | Trial completion date: Dec 2022 --> Dec 2023

Gliomas are the most prevalent type of brain tumor in the central nervous system. These findings are consistent with our previous study, which investigated the MRS-detectable consequences of two other mutant IDH inhibitors: AG120 and AG881. Collectively, our work identifies translatable MRS-based metabolic biomarkers of mutant IDH1 inhibition.

P1, N=81, Active, not recruiting, Bayer | Trial completion date: Dec 2021 --> Dec 2022

Several mutant IDH inhibitors are currently in clinical trials, including AG-881 and BAY-1436032. Importantly, all models demonstrated enhanced animal survival following both treatments and the metabolic alterations were observed prior to any detectable differences in tumor volume between control and treated tumors. Our study therefore identifies potential translatable early metabolic biomarkers of drug delivery, mutant IDH inhibition and glioma response to treatment with emerging clinically relevant therapies.

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

P1, N=81, Active, not recruiting, Bayer | Trial completion date: Mar 2021 --> Dec 2021

P1, N=81, Active, not recruiting, Bayer | Trial completion date: Dec 2020 --> Mar 2021

Non-invasive monitoring of mIDH1 inhibition by BAY1436032 in mIDH1 gliomas is feasible.

On the other hand, presence of IDH1R132H led to a suppression in baseline expression of key innate immune players, which could be rescued by the mutant IDH1 inhibitor, BAY-1436032...Our data indicates the presence of an interplay between IDH1 and ATRX mutations that may regulate innate signaling in gliomas. Understanding the mechanisms governing this interplay may aid in designing therapies that exploit this interplay.

P1; Trial completion date: Jun 2020 --> Dec 2020

This strong synergy is mediated through inhibition of MAPK/ERK and RB/E2F signaling. Our data strongly argues for the concurrent application of mIDH1 inhibitors and azacitidine and predicts improved outcome of this regimen in IDH1 mutated AML patients.

P1; Trial completion date: Dec 2019 --> Jun 2020

P1; Trial completion date: Jun 2019 --> Dec 2019

P2, N=27, Completed, Bayer | Active, not recruiting --> Completed

P2, N=27, Active, not recruiting, Bayer | Trial completion date: Oct 2019 --> Mar 2019

P2; N=27; Active, not recruiting; Sponsor: Bayer; N=80 --> 27; Trial primary completion date: Aug 2019 --> Dec 2018; Recruiting --> Active, not recruiting

P1; Trial primary completion date: Mar 2019 --> Nov 2018

P1; Recruiting --> Active, not recruiting