Delving into the Latest Updates on Miptenalimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

LAG3

Action

inhibitors

Mechanism

LAG3 inhibitors(Lymphocyte activation gene 3 protein inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [3]

Active Indication

Adenocarcinoma of EsophagusAdvanced cancerAdvanced Endometrial Carcinoma+ [5]

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaSquamous Cell Carcinoma of Head and Neck

Originator Organization

Boehringer Ingelheim GmbH

Active Organization

Boehringer Ingelheim GmbH

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 26034805L

Source: *****

Sequence Code 26034799H

Source: *****

This study has 2 parts. The first part of the study is done. The first part was open to adults with different types of advanced cancer (solid tumors). The second part is open to people with specific types of soft tissue sarcoma, advanced lung cancer, and cancer in the stomach, bladder or bile ducts.
The participants get a combination of 2 medicines called brigimadlin (also called BI 907828) and ezabenlimab (also called BI 754091). Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). When the study started, some participants got a third medicine called BI 754111 in addition. Treatment with BI 754111 was stopped because data from another study showed no additional effect of BI 754111.
The purpose of the first part of the study was to find out the highest dose of brigimadlin that the participants could tolerate in combination with ezabenlimab. This dose is used in the second part of the study.
The purpose of the second part is to see whether the combination of brigimadlin with ezabenlimab is able to make tumors shrink.
The participants are in the study as long as they benefit from treatment and can tolerate it.
Ezabenlimab treatment is limited to 2 years. During this time, they get infusions of ezabenlimab, and take tablets with brigimadlin every 3 weeks. The doctors check how many participants have health problems during the study. The doctors also monitor the size of the tumor.

Start Date20 Jun 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT03697304

/ CompletedPhase 2

An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 (Ezabenlimab) Anti-PD-1 Based Combination Regimens in PD-(L)1 naïve and PD-(L)1 Pretreated Patient Populations With Advanced and/or Metastatic Solid Tumours Who Have Had at Least One Line of Systemic Therapy

This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Such therapies are also called immune checkpoint inhibitors.
How long the participants are in the study depends on whether they benefit from treatment and whether they experience unacceptable side effects. The participants are put into different groups.
Each group receives BI 754091 in combination with another medicine.
The doctors check whether the tumors shrink or disappear. The doctors also check the general health of the participants.

Start Date19 Mar 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT03780725

/ TerminatedPhase 1

An Open Label Phase I PET Imaging Study to Investigate the Bio-distribution and Tumor Uptake of [89Zr]Zr-BI 754111 in Patients With Advanced Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Treated With BI 754111 in Combination With BI 754091

The main objective of this study is to determine the biodistribution and intra-tumor accumulation of [89Zr]Zr-BI 754111 at baseline and its change upon treatment

Start Date22 Jan 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Miptenalimab

Login to view more data

100 Translational Medicine associated with Miptenalimab

Login to view more data

100 Patents (Medical) associated with Miptenalimab

Login to view more data

6

Literatures (Medical) associated with Miptenalimab

01 Mar 2025·CPT: Pharmacometrics & Systems Pharmacology

A minimal physiologically‐based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti‐LAG‐3 monoclonal antibody

Article

Author: Huisman, Marc C. ; Pérez‐Pitarch, Alejandro ; Menke‐van der Houven van Oordt, C. Willemien ; Montaseri, Ghazal ; Miedema, Iris H. C. ; Thiele, Andrea ; Michelet, Robin ; Busse, David ; Petersson, Klas

AbstractIn oncology drug development, measuring drug concentrations at the tumor site and at the targeted receptor remains an ongoing challenge. Positron emission tomography (PET)‐imaging is a promising noninvasive method to quantify intratumor exposure of a radiolabeled drug (biodistribution data) and target saturation by treatment doses in vivo. Here, we present the development and application of a minimal physiologically‐based pharmacokinetic (mPBPK) modeling approach to integrate biodistribution data in a quantitative platform to characterize and predict intratumor exposure and receptor occupancy (RO) of BI 754111, an IgG‐based anti‐lymphocyte‐activation gene 3 (LAG‐3) monoclonal antibody (mAb). Specifically, calibration and qualification of the predictions were performed using 89Zr‐labeled BI 754111 biodistribution data, that is, PET‐derived intratumor drug concentration data, tumor‐to‐plasma ratios, and data from Patlak analyses. The model predictions were refined iteratively by the inclusion of additional biological processes into the model structure and the use of sensitivity analyses to assess the impact of model assumptions and parameter uncertainty on the predictions and model robustness. The developed mPBPK model allowed an adequate description of observed tumor radioactivity concentrations and tumor‐to‐plasma ratios leading to subsequent adequate prediction of LAG‐3 RO at different dose levels. In the future, the developed model could be used as a platform for the prediction and analysis of biodistribution data for other mAbs and may ultimately support dose optimization by identifying dosages resulting in saturated RO.

01 Jun 2023·European Journal of Nuclear Medicine and Molecular Imaging

89Zr-immuno-PET using the anti-LAG-3 tracer [89Zr]Zr-BI 754111: demonstrating target specific binding in NSCLC and HNSCC

Article

Author: Thiele, Andrea ; Hesse, Raphael ; Grempler, Rolf ; Menke-van der Houven van Oordt, C Willemien ; de Gruijl, Tanja D ; Bahce, Idris ; Peltzer, Alexander ; Huisman, Marc C ; van Dongen, Guus A M S ; Elgadi, Mabrouk ; Vugts, Danielle J ; Pitarch, Alejandro Perez ; Miedema, Iris H C ; Zwezerijnen, Gerben J C

AbstractPurposeAlthough lymphocyte activation gene-3 (LAG-3) directed therapies demonstrate promising clinical anti-cancer activity, only a subset of patients seems to benefit and predictive biomarkers are lacking. Here, we explored the potential use of the anti-LAG-3 antibody tracer [89Zr]Zr-BI 754111 as a predictive imaging biomarker and investigated its target specific uptake as well as the correlation of its tumor uptake and the tumor immune infiltration.MethodsPatients with head and neck (N = 2) or lung cancer (N = 4) were included in an imaging substudy of a phase 1 trial with BI 754091 (anti-PD-1) and BI 754111 (anti-LAG-3). After baseline tumor biopsy and [18F]FDG-PET, patients were given 240 mg of BI 754091, followed 8 days later by administration of [89Zr]Zr-BI 754111 (37 MBq, 4 mg). PET scans were performed 2 h, 96 h, and 144 h post-injection. To investigate target specificity, a second tracer administration was given two weeks later, this time with pre-administration of 40 (N = 3) or 600 mg (N = 3) unlabeled BI 754111, followed by PET scans at 96 h and 144 h post-injection. Tumor immune cell infiltration was assessed by immunohistochemistry and RNA sequencing.ResultsTracer uptake in tumors was clearly visible at the 4-mg mass dose (tumor-to-plasma ratio 1.63 [IQR 0.37-2.89]) and could be saturated by increasing mass doses (44 mg: 0.67 [IQR 0.50–0.85]; 604 mg: 0.56 [IQR 0.42–0.75]), demonstrating target specificity. Tumor uptake correlated to immune cell-derived RNA signatures.Conclusions[89Zr]Zr-BI-754111 PET imaging shows favorable technical and biological characteristics for developing a potential predictive imaging biomarker for LAG-3-directed therapies.Trial registrationClinicalTrials.gov, NCT03780725. Registered 19 December 2018

31 Dec 2022·OncoImmunology

Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses

Article

Author: Wurm, Melanie ; Sedgwick, Jonathon D. ; Thibodeau, Michael ; Oquendo Cifuentes, Elisa ; Vogt, Anne ; Lorenz, Ivo C. ; Apfler, Ilse ; Mostböck, Sven ; Zettl, Markus ; Frego, Lee ; Moll, Jürgen ; Schaaf, Otmar ; Reschke, Markus ; Kenny, Cynthia ; Kraut, Norbert ; Waizenegger, Irene C. ; Tirapu, Iñigo

Upregulation of inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3), may limit the antitumor activity of therapeutic antibodies targeting the programmed cell death protein-1 (PD-1) pathway. We describe the binding properties of ezabenlimab, an anti-human PD-1 antibody, and BI 754111, an anti-human LAG-3 antibody, and assess their activity alone and in combination. Ezabenlimab bound with high affinity to human PD-1 (K_D = 6 nM) and blocked the interaction of PD-1 with PD-L1 and PD-L2. Ezabenlimab dose-dependently increased interferon-γ secretion in human T cells expressing PD-1 in co-culture with PD-L1-expressing dendritic cells. Administration of ezabenlimab to human PD-1 knock-in mice dose-dependently inhibited growth of MC38 tumors. To reduce immunogenicity, ezabenlimab was reformatted from a human IgG4 to a chimeric variant with a mouse IgG1 backbone (BI 905725) for further in vivo studies. Combining BI 905725 with anti-mouse LAG-3 antibodies improved antitumor activity versus BI 905725 monotherapy in the MC38 tumor model. We generated BI 754111, which bound with high affinity to human LAG-3 and prevented LAG-3 interaction with its ligand, major histocompatibility complex class II. In an in vitro model of antigen-experienced memory T cells expressing PD-1 and LAG-3, interferon-γ secretion increased by an average 1.8-fold versus isotype control (p = 0.027) with BI 754111 monotherapy, 6.9-fold (p < 0.0001) with ezabenlimab monotherapy and 13.2-fold (p < 0.0001) with BI 754111 plus ezabenlimab. Overall, ezabenlimab and BI 754111 bound to their respective targets with high affinity and prevented ligand binding. Combining ezabenlimab with BI 754111 enhanced in vitro activity versus monotherapy, supporting clinical investigation of this combination (NCT03156114; NCT03433898).

100 Deals associated with Miptenalimab

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
Adenocarcinoma of Esophagus	Phase 2	United States	Boehringer Ingelheim GmbH	19 Mar 2019
Adenocarcinoma of Esophagus	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	19 Mar 2019
Adenocarcinoma of Esophagus	Phase 2	Canada	Boehringer Ingelheim GmbH	19 Mar 2019
Advanced cancer	Phase 2	United States	Boehringer Ingelheim GmbH	19 Mar 2019
Neoplasm Metastasis	Phase 2	United States	Boehringer Ingelheim GmbH	19 Mar 2019
Neoplasm Metastasis	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	19 Mar 2019
Neoplasm Metastasis	Phase 2	Canada	Boehringer Ingelheim GmbH	19 Mar 2019
Non-Small Cell Lung Cancer	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	19 Mar 2019
Non-Small Cell Lung Cancer	Phase 2	Canada	Boehringer Ingelheim GmbH	19 Mar 2019
Non-Small Cell Lung Cancer	Phase 2	United States	Boehringer Ingelheim GmbH	19 Mar 2019

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03449381 \| NCT03964233 (ASCO_GI2023) Manual	Phase 1	Advanced Bile Duct Carcinoma MDM2 Expression	8	BI 907828	(fnyknigrtb) = zuarkcnhcu mvzqlslhpr (tvswfevvoy ) View more	Positive	24 Jan 2023
				BI 907828+Ezabenlimab 240 mg±BI 754111	(wyscbgwuhs) = mbqznrtdjo grcqcpvdnu (bazsdlorsy ) View more
NCT03964233 (ASCO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	26	BI 907828+ezabenlimab+BI 754111	(xnnaxkpunq) = kqdqidkywc tmmxzbkiag (xltmllsyka ) View more	Positive	02 Jun 2022
				BI 907828+ezabenlimab	(xnnaxkpunq) = ooensbgtph tmmxzbkiag (xltmllsyka ) View more
NCT03433898 (ASCO_GI 12021 \| ASCO_GI 22021) Manual	Phase 1	Esophageal Carcinoma \| Gastrooesophageal junction cancer \| Stomach Cancer	73	BI 754091+BI 754111 (gastric/gastroesophageal junction cancer (Cohort A))	(ejevqxhbtk) = nngptgdjvl gccmrpgyte (zwamqybqso ) View more	Positive	20 Jan 2021
				BI 754091+BI 754111 (esophageal cancer (Cohort B))	(ejevqxhbtk) = vnoesbyzdv gccmrpgyte (zwamqybqso ) View more
NCT03156114 (AACR2020)	Phase 1	Metastatic Colorectal Carcinoma	40	BI 754111 600 mg + BI 754091 240 mg	(xoujnumrve) = oxgdfncyuv cdlpleptff (hxixkthunp ) View more	Positive	15 Aug 2020
NCT03433898 (ASCO 12020 \| ASCO 22020) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	121	BI 754091+BI 754111 (gastric/esophagogastric junction cancer)	(furygzdtil) = zhmwzovfxf aqlvdeisjj (jhhmdzyfyn ) View more	Positive	29 May 2020
				BI 754091+BI 754111 (esophageal cancer)	(furygzdtil) = itudtlzcxv aqlvdeisjj (jhhmdzyfyn ) View more
NCT03156114 (ESMO2018)	Phase 1	Solid tumor \| Advanced Malignant Solid Neoplasm \| Non-Small Cell Lung Cancer \| Metastatic Microsatellite Stable Colorectal Carcinoma	172	BI 754111	qcaoppufez(fwcbmgngtq) = lutitzgvwb zobptwybfd (ygkbzqxwam )	-	20 Oct 2018
				BI 754091	qcaoppufez(fwcbmgngtq) = oeghkgyaie zobptwybfd (ygkbzqxwam )
NCT03156114 (AACR2018)	Phase 1	Advanced Malignant Solid Neoplasm \| Non-Small Cell Lung Cancer \| Advanced cancer	172	BI 754111	pskyfjjmvy(xywqeipbtv) = pjlgflszvl bosevwumhi (rvjgdtjnou )	-	01 Jul 2018
				BI 754091	pskyfjjmvy(xywqeipbtv) = euuypdcvxh bosevwumhi (rvjgdtjnou )

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

login

or

view full example data