Delving into the Latest Updates on BAY-1436032 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

IDH1

Mechanism

IDH1 inhibitors(Isocitrate dehydrogenase [NADP] cytoplasmic inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Advanced Malignant Solid Neoplasm

Inactive Indication

Acute Myeloid Leukemia

Originator Organization

Bayer AG

Active Organization

Bayer AG

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC26H30F3N3O3

InChIKeyRNMAUIMMNAHKQR-QFBILLFUSA-N

CAS Registry1803274-65-8

An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated and / or Recommended Phase II Dose of Oral Mutant IDH1 (mIDH1) Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Efficacy in Patients With mIDH1-R132X Advanced Acute Myeloid Leukemia (AML)

To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)

Start Date14 Jun 2017

Sponsor / Collaborator

Bayer AG

NCT02746081 / Active, not recruitingPhase 1

An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated or Recommended Phase II Dose of Oral Mutant IDH1 Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamic and Anti-tumor Activity in Patients With IDH1-R132X-mutant Advanced Solid Tumors

The primary objective of this study is:
- Determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of BAY 1436032 in patients with isocitrate dehydrogenase-1 (IDH1)-R132X-mutant advanced solid tumors.
The secondary objectives of this study are:
* Evaluate the pharmacokinetics (PK) of BAY1436032 in patients with IDH1-R132X-mutant advanced solid tumors.
* Evaluate the effect of a standard high-fat, high calorie meal on the PK of BAY1436032.
* Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY1436032 administration in patients with IDH1-R132X-mutant advanced solid tumors.

Start Date26 May 2016

Sponsor / Collaborator

Bayer AG

100 Clinical Results associated with BAY-1436032

Login to view more data

100 Translational Medicine associated with BAY-1436032

Login to view more data

100 Patents (Medical) associated with BAY-1436032

Login to view more data

10

Literatures (Medical) associated with BAY-1436032

01 Jan 2023·Neuro-Oncology Advances

Monitoring response to a clinically relevant IDH inhibitor in glioma—Hyperpolarized 13C magnetic resonance spectroscopy approaches

Article

Author: Minami, Noriaki ; Wu, Jing ; Ronen, Sabrina M ; Kim, Yaewon ; Cherukuri, Murali Krishna ; Swenson, Rolf E ; Mushti, Chandrasekhar ; Hong, Donghyun ; Vigneron, Daniel B

AbstractBackgroundMutant isocitrate dehydrogenase (IDHmut) catalyzes 2-hydroxyglutarate (2HG) production and is considered a therapeutic target for IDHmut tumors. However, response is mostly associated with inhibition of tumor growth. Response assessment via anatomic imaging is therefore challenging. Our goal was to directly detect IDHmut inhibition using a new hyperpolarized (HP) 13C magnetic resonance spectroscopy-based approach to noninvasively assess α-ketoglutarate (αKG) metabolism to 2HG and glutamate.MethodsWe studied IDHmut-expressing normal human astrocyte (NHAIDH1mut) cells and rats with BT257 tumors, and assessed response to the IDHmut inhibitor BAY-1436032 (n ≥ 4). We developed a new 13C Echo Planar Spectroscopic Imaging sequence with an optimized RF pulse to monitor the fate of HP [1-13C]αKG and [5-12C,1-13C]αKG with a 2.5 × 2.5 × 8 mm3 spatial resolution.ResultsCell studies confirmed that BAY-1436032-treatment leads to a drop in HP 2HG and an increase in HP glutamate detectable with both HP substrates. Data using HP [5-12C,1-13C]αKG also demonstrated that its conversion to 2HG is detectable without the proximal 1.1% natural abundance [5-13C]αKG signal. In vivo studies showed that glutamate is produced in normal brains but no 2HG is detectable. In tumor-bearing rats, we detected the production of both 2HG and glutamate, and BAY-1436032-treatment led to a drop in 2HG and an increase in glutamate. Using HP [5-12C,1-13C]αKG we detected metabolism with an signal-to-noise ratio of 23 for 2HG and 17 for glutamate.ConclusionsOur findings point to the clinical potential of HP αKG, which recently received FDA investigational new drug approval for research, for noninvasive localized imaging of IDHmut status.

15 May 2021·Clinical Cancer ResearchQ1 · MEDICINE

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

Q1 · MEDICINE

Article

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

AbstractPurpose: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.

01 Nov 2020·LeukemiaQ1 · MEDICINE

Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results

Q1 · MEDICINE

Article

Author: Silverman, Lewis R ; Wang, Eunice S ; Jeffers, Michael ; Mims, Alice ; Palmisiano, Neil ; Wu, Bingyan ; Cai, Charles ; Kaulfuss, Stefan ; DiNardo, Courtney ; Baldus, Claudia ; Mantzaris, Ioannis ; Wagner, Markus ; Perl, Alexander E ; Schwind, Sebastian ; Fiedler, Walter ; Lagkadinou, Eleni ; Krämer, Alwin ; Genvresse, Isabelle ; Heuser, Michael ; Pardee, Timothy ; Wilkinson, Gary ; Rentzsch, Christine

AbstractThe mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing. Most subjects experienced only partial target inhibition as indicated by plasma R-2HG levels. BAY1436032 was safe and a maximum tolerated dose was not identified. The median treatment duration for all subjects was 3.0 months (0.49–8.5). The overall response rate was 15% (4/27; 1 CRp, 1 PR, 2 MLFS), with responding subjects experiencing a median treatment duration of 6.0 months (3.9–8.5) and robust R-2HG decreases. Thirty percent (8/27) achieved SD, with a median treatment duration of 5.5 months (3.1–7.0). Degree of R-2HG inhibition and clinical benefit did not correlate with dose. Although BAY1436032 was safe and modestly effective as monotherapy, the low overall response rate and incomplete target inhibition achieved at even the highest dose tested do not support further clinical development of this investigational agent in AML.

100 Deals associated with BAY-1436032

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 1	US	Bayer AG	14 Jun 2017
Acute Myeloid Leukemia	Phase 1	DE	Bayer AG	14 Jun 2017
Advanced Malignant Solid Neoplasm	Phase 1	DE	Bayer AG	26 May 2016
Advanced Malignant Solid Neoplasm	Phase 1	DK	Bayer AG	26 May 2016
Advanced Malignant Solid Neoplasm	Phase 1	JP	Bayer AG	26 May 2016
Advanced Malignant Solid Neoplasm	Phase 1	US	Bayer AG	26 May 2016

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03127735 (Pubmed \| Leukemia) Manual	Phase 1	Acute Myeloid Leukemia IDH1 Mutation	27	BAY1436032	(efdgnanyhf) = not identified thviwqfmsu (ktwwndpcvv )	Negative	01 Nov 2020
EHA2020	Phase 1	IDH1 Mutation Acute Myeloid Leukemia	27	BAY1436032	(juhlesbdfh) = 33% rvyqyvdukh (clwsrydujk ) View more	Positive	14 May 2020
AACR2016	Phase 1	-	-	BAY 1436032	czfafxsylq(dpelhuslkk) = xqtzxyfmch icpoxyaqxb (eiohxovjdx )	Positive	15 Jul 2016