Delving into the Latest Updates on Miptenalimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

LAG3

Mechanism

LAG3 inhibitors(Lymphocyte activation gene 3 protein inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Advanced Malignant Solid NeoplasmAdvanced cancerNon-Small Cell Lung Cancer

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-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Gene 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 Date11 Jun 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT03697304 / Active, not recruitingPhase 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 Date12 Feb 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Miptenalimab

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100 Translational Medicine associated with Miptenalimab

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100 Patents (Medical) associated with Miptenalimab

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4

Literatures (Medical) associated with Miptenalimab

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).

OncoTargets and Therapy

Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series

Author: Lugowska, Iwona ; Geng, Junxian ; LoRusso, Patricia ; Hafez, Navid ; Li, Jian ; Ramlau, Rodryg ; Teufel, Michael ; Märten, Angela ; Macarulla, Teresa ; Yamamoto, Noboru ; Tolcher, Anthony

BackgroundIn patients with advanced biliary tract cancer (BTC), first-line chemotherapy plus immunotherapy has improved outcomes; however, second-line options that reflect the disease's molecular heterogeneity are still needed. One emerging target is MDM2, amplified in ~5-8% of BTC cases.MethodsThis is a subset analysis of two ongoing Phase Ia/Ib trials assessing patients treated with brigimadlin (BI 907828; a highly potent, oral MDM2-p53 antagonist) ± ezabenlimab (PD-1 inhibitor) ± BI 754111 (anti-LAG-3; n = 1).ResultsResults from 12 patients with BTC are shown (monotherapy: n = 6/combination: n = 6). Six patients achieved partial response (monotherapy: n = 2/combination: n = 4), four had stable disease; responses were durable. Brigimadlin had a manageable safety profile. Seven patients had dose reductions due to adverse events, but no treatment-related adverse events led to treatment discontinuation.ConclusionBrigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation.

100 Deals associated with Miptenalimab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 2	GB	Boehringer Ingelheim GmbH	01 May 2019
Advanced cancer	Phase 1	PL	Boehringer Ingelheim GmbH	13 Jun 2017
Advanced cancer	Phase 1	US	Boehringer Ingelheim GmbH	13 Jun 2017
Advanced cancer	Phase 1	GB	Boehringer Ingelheim GmbH	13 Jun 2017
Advanced cancer	Phase 1	ES	Boehringer Ingelheim GmbH	13 Jun 2017
Advanced cancer	Phase 1	CA	Boehringer Ingelheim GmbH	13 Jun 2017
Non-Small Cell Lung Cancer	Phase 1	GB	Boehringer Ingelheim GmbH	13 Jun 2017
Non-Small Cell Lung Cancer	Phase 1	CA	Boehringer Ingelheim GmbH	13 Jun 2017
Non-Small Cell Lung Cancer	Phase 1	ES	Boehringer Ingelheim GmbH	13 Jun 2017
Non-Small Cell Lung Cancer	Phase 1	US	Boehringer Ingelheim GmbH	13 Jun 2017

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Clinical Result

Indication

Phase

Evaluation

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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	(mpqbzglpgp) = ihlphdisik oqxzzopoym (mydjyqnbiy ) View more	Positive	24 Jan 2023
				BI 907828+Ezabenlimab 240 mg±BI 754111	(mhptwpfhpe) = tpqcwhamtr kjzzdjtgce (qipbwlofwl ) View more
NCT03964233 (ASCO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	26	BI 907828+ezabenlimab+BI 754111	(khmtxxqibz) = czvmuzkxxw vkoiylirya (parmzddyra ) View more	Positive	02 Jun 2022
				BI 907828+ezabenlimab	(khmtxxqibz) = xajdzwmlzr vkoiylirya (parmzddyra ) View more
NCT03433898 (ASCO_GI2021) Manual	Phase 1	Esophageal Carcinoma \| Gastrooesophageal junction cancer \| Stomach Cancer	73	BI 754091+BI 754111 (gastric/gastroesophageal junction cancer (Cohort A))	(fssedqlprb) = wfngjxoged ecsjtaaalo (sudtkobbsc ) View more	Positive	20 Jan 2021
				BI 754091+BI 754111 (esophageal cancer (Cohort B))	(fssedqlprb) = ihzarolbuu ecsjtaaalo (sudtkobbsc ) View more
NCT03156114 (AACR2020)	Phase 1	Metastatic Colorectal Carcinoma	40	BI 754111 600 mg + BI 754091 240 mg	(bqfpjapfju) = qfelqmnaez ytywykcvzq (svrwzuwiee ) View more	Positive	15 Aug 2020
NCT03433898 (ASCO2020) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	121	BI 754091+BI 754111 (gastric/esophagogastric junction cancer)	(zlgjnmxgre) = xwbihjrbjo hflqoynexl (whcgpvynri ) View more	Positive	29 May 2020
				BI 754091+BI 754111 (esophageal cancer)	(zlgjnmxgre) = vnixknmswj hflqoynexl (whcgpvynri ) 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	wtkavztzas(lkgtkhsoyo) = tkjcfxseie nddsfiomvn (cqakhgongw )	-	20 Oct 2018
				BI 754091	wtkavztzas(lkgtkhsoyo) = vxwarzhrqc nddsfiomvn (cqakhgongw )
NCT03156114 (AACR2018)	Phase 1	Advanced Malignant Solid Neoplasm \| Non-Small Cell Lung Cancer \| Advanced cancer	172	BI 754111	qopwqpfhon(yocmpqrjpw) = jdybpmsooi owzujrtpju (qvdqipbvyr )	-	01 Jul 2018
				BI 754091	qopwqpfhon(yocmpqrjpw) = jcvyfnojzt owzujrtpju (qvdqipbvyr )