Delving into the Latest Updates on Lirilumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-KIR (1-7F9), Anti-KIR monoclonal antibody, Lirilumab (USAN/INN)

+ [8]

Target

KIR2DL1 x KIR2DL2 x KIR2DL3 x KIR2DS1 x KIR2DS2

Mechanism

KIR2DL1 antagonists(Killer cell immunoglobulin-like receptor 2DL1 antagonists), KIR2DL2 antagonists(Killer cell immunoglobulin-like receptor 2DL2 antagonists), KIR2DL3 antagonists(Killer cell immunoglobulin-like receptor 2DL3 antagonists)

+ [2]

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Recurrent Squamous Cell Carcinoma of the Head and NeckBladder Cancer

Inactive Indication

Acute Myeloid LeukemiaAdvanced cancerAdvanced Malignant Solid Neoplasm+ [5]

Originator Organization

Innate Pharma SA

Active Organization

Bristol Myers Squibb Co.

Ono Pharmaceutical Co., Ltd.

Inactive Organization

Innate Pharma SA

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 1260L

Source: *****

Sequence Code 10125384H

Source: *****

A Phase 1 Study of the Safety and Pharmacokinetics of Anti-KIR Monoclonal Antibody (Lirilumab, BMS-986015) in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab,BMS-936558) or in Combination With Nivolumab and Anti-CTLA-4 Monoclonal Antibody (Ipilimumab, BMS-734016) in Advanced and/or Metastatic Solid Tumors

The purpose of this study is to determine whether lirilumab in combination with nivolumab or in combination with nivolumab and ipilimumab is safe in the treatment of advanced and/or metastatic solid tumors

Start Date14 Jul 2017

Sponsor / Collaborator

Bristol Myers Squibb Co.

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100 Clinical Results associated with Lirilumab

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100 Translational Medicine associated with Lirilumab

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100 Patents (Medical) associated with Lirilumab

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40

Literatures (Medical) associated with Lirilumab

01 Aug 2024·European Urology Oncology

PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy

Article

Author: Li-Ning-Tapia, Elsa ; Koshkin, Vadim S ; Galsky, Matthew D ; Hahn, Noah M ; Sundi, Debasish ; Chu, Xiangying ; Grivas, Petros ; Carducci, Michael A ; Cole, Suzanne ; Gartrell, Benjamin A ; Cetnar, Jeremy P ; Jain, Rohit K ; Woo, Brianna ; Dreicer, Robert

BACKGROUND AND OBJECTIVENeoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility.METHODSPatients with localized MIBC received two doses of nivolumab (480 mg) alone (cohort 1) or with lirilumab (240 mg; cohort 2) prior to RC. Cohorts were enrolled sequentially. The key eligibility criteria were cT2-4aN0-1M0 stage and cisplatin ineligibility/refusal. The primary endpoint was the rate of grade (G) ≥3 treatment-related adverse events (TRAEs) as per Common Terminology Criteria for Adverse Events version 5.0. The key secondary endpoints included the proportion of patients who underwent RC >6 wk after the last dose, CD8+ T-cell density change between pretreatment transurethral resection of bladder tumor (TURBT) and post-treatment RC, ypT0N0, KEY FINDINGS AND LIMITATIONSAmong 43 patients enrolled (n = 13, cohort 1; n = 30, cohort 2), 13 and 29 completed intended neoadjuvant therapy, respectively, in cohorts 1 and 2, and 41 underwent RC. The median time from the last dose to RC was 4 wk. The G3 TRAEs occurred in 0% (90% confidence interval [CI] 0-21%) of patients in cohort 1 and 7% (90% CI 1-20%) in cohort 2; all these TRAEs resolved and no G4/5 TRAEs occurred. No patient had delayed RC for >6 wk. In cohorts 1 and 2, ypT0N0 rates for patients with MIBC and RC were 17% and 21%, CONCLUSIONS AND CLINICAL IMPLICATIONSNeoadjuvant nivolumab-based immunotherapy was safe, feasible, and well tolerated in cisplatin-ineligible patients with MIBC. Although ypT0N0 rates were lower than expected, 2-yr survival rates seem to be comparable with those of other neoadjuvant immunotherapy trials. Nivolumab is being evaluated in the CA-017-078 trial (NCT03661320).PATIENT SUMMARYFor patients with muscle-invasive bladder cancer unable to receive cisplatin-based chemotherapy, treatment with nivolumab without and with lirilumab prior to radical cystectomy was safe, feasible, and well tolerated. Nivolumab-based immunotherapy showed lower pathologic response rates than but similar survival rates to other neoadjuvant immunotherapy trials.

01 Jul 2024·Journal for ImmunoTherapy of Cancer

IFNγ mediates the resistance of tumor cells to distinct NK cell subsets

Article

Author: Ng, Siu Wang ; Hofman, Tomáš ; Cerwenka, Adelheid ; Heigwer, Florian ; Garcés-Lázaro, Irene ; Boutros, Michael

BackgroundImmune checkpoint blockade targeting the adaptive immune system has revolutionized the treatment of cancer. Despite impressive clinical benefits observed, patient subgroups remain non-responsive underscoring the necessity for combinational therapies harnessing additional immune cells. Natural killer (NK) cells are emerging tools for cancer therapy. However, only subpopulations of NK cells that are differentially controlled by inhibitory receptors exert reactivity against particular cancer types. How to leverage the complete anti-tumor potential of all NK cell subsets without favoring the emergence of NK cell-resistant tumor cells remains unresolved.MethodsWe performed a genome-wide CRISPR/Cas9 knockout resistance screen in melanoma cells in co-cultures with human primary NK cells. We comprehensively evaluated factors regulating tumor resistance and susceptibility by focusing on NK cell subsets in an allogenic setting. Moreover, we tested therapeutic blocking antibodies currently used in clinical trials.ResultsMelanoma cells deficient in antigen-presenting or the IFNγ-signaling pathways were depleted in remaining NK cell-co-cultured melanoma cells and displayed enhanced sensitivity to NK cells. Treatment with IFNγ induced potent resistance of melanoma cells to resting, IL-2-cultured and ADCC-activated NK cells that depended onB2Mrequired for the expression of both classical and non-classical MHC-I. IFNγ-induced expression of HLA-E mediated the resistance of melanoma cells to the NKG2A+KIR−and partially to the NKG2A+KIR+NK cell subset. The expression of classical MHC-I by itself was sufficient for the inhibition of the NKG2A−KIR+, but not the NKG2A+KIR+NK cell subset. Treatment of NK cells with monalizumab, an NKG2A blocking mAb, enhanced the reactivity of a corresponding subset of NK cells. The combination of monalizumab with lirilumab, blocking KIR2 receptors, together with DX9, blocking KIR3DL1, was required to restore cytotoxicity of all NK cell subsets against IFNγ-induced resistant tumor cells in melanoma and tumors of different origins.ConclusionOur data reveal that in the context of NK cells, IFNγ induces the resistance of tumor cells by the upregulation of classical and non-classical MHC-I. Moreover, we reveal insights into NK cell subset reactivity and propose a therapeutic strategy involving combinational monalizumab/lirilumab/DX9 treatment to fully restore the antitumor response across NK cell subsets.

16 Sep 2023·International journal of molecular sciences

Therapeutic Anti-KIR Antibody of 1-7F9 Attenuates the Antitumor Effects of Expanded and Activated Human Primary Natural Killer Cells on In Vitro Glioblastoma-like Cells and Orthotopic Tumors Derived Therefrom.

Article

Author: Nishimura, Fumihiko ; Nakazawa, Tsutomu ; Tsujimura, Takahiro ; Morimoto, Takayuki ; Nakase, Hiroyuki ; Maeoka, Ryosuke ; Shida, Yoichi ; Nakamura, Mitsutoshi ; Park, Young-Soo ; Nakagawa, Ichiro ; Matsuda, Ryosuke ; Yamada, Shuichi

Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs.

1

News (Medical) associated with Lirilumab

06 Oct 2021

·www.biospace.com

Natural Killer (NK) Cell Therapeutics Market: Cancer Segment to Offer Attractive Opportunities

Natural Killer (NK) Cell: Introduction Natural killer (NK) cells also known as K cells or killer cells. These are a type of white blood cells (lymphocyte) and a component of the innate immune system. Natural killer cells play an important role in the host rejection of virally infected cells and tumors. Natural killer cells are cytotoxic. Small granules in natural killer cell cytoplasm contain special proteins, such as proteases and perforin known as granzymes. Once the foreign cell reaches the proximity of the natural killer cell, the natural killer cells attack the foreign cells by releasing protein including perforin that forms stomas in the cell membrane of the target cell through which the associated molecules and granzymes can enter and then induces apoptosis. Natural killer cells are activated in response to macrophage-derived cytokines and interferons. Patient deficient in natural killer cells is highly prone to early phases of the herpes virus infection. Request Brochure of Report - Key Drivers of Global Natural Killer (NK) Cell Therapeutics Market The global natural killer (NK) cell therapeutics market is primarily driven by increase in usage of natural killer cells for the treatment of liver and infectious diseases across the globe. According to the Centers for Disease Control and Prevention, in the U.S., in 2016, deaths due to tuberculosis stood at 9,272, salmonella claimed 53,850 lives, Lyme disease caused 36,429 deaths, and 375 people died due to the meningococcal disease. The number of patient visits to physician with parasitic and infectious as the primary diagnosis was reported to be 15.5 million in the U.S. in the same year. Increase in patient population with infectious and liver diseases is a key driver of the global natural killer (NK) cell therapeutics market Rise in the awareness among the population about various immunotherapies and increase in research and development of bi-specific antibody for engaging natural killer cells to eliminate tumor cells are driving the global natural killer (NK) cell therapeutics market Request for Analysis of COVID-19 Impact on Natural Killer (NK) Cell Therapeutics Market – Natural Killer (NK) Cell Directed Antibodies Segment Held Major Share of Global Market Based on type, the global natural killer (NK) cell therapeutics market can be divided into natural killer (NK) cell therapies and natural killer (NK) cell directed antibodies Natural killer (NK) cell therapies segment can be further divided into CNDO-109, oNKord, natural killer cells, and others Natural killer (NK) cell directed antibodies segment can sub-divided into MOGAMULIZUMAB, Lirilumab, AFM13, NKTT 120, and others Natural killer (NK) cell directed antibodies segment accounted for a major market share in 2018. The dominance of the segment can be attributed to increase in the use of monoclonal antibodies (mAbs) for various diseases and easy availability of these drugs. Pre book Natural Killer (NK) Cell Therapeutics Market Report at Cancer Segment to Offer Attractive Opportunities In terms of application, the global natural killer (NK) cell therapeutics market can be classified into gastrointestinal diseases, immune-proliferative disorders, cancer, and others Cancer segment is expected to account for a major share of the global natural killer (NK) cell therapeutics market in 2027 The dominance of this segment can be attributed to the increase in prevalence rate of cancer across the globe Read More Information: Top of Form ReadR Key Players Operating in Global Market The global natural killer (NK) cell therapeutics market is highly consolidated with presence of few players accounting for the majority of the market share. Key players operating in the global natural killer (NK) cell therapeutics market are: Affimed Celgene Corporation Glycostem Nkarta Therapeutics Innate Pharma S.A Ziopharm Oncology, Inc. NantKwest NKT Therapeutics Inc. Fate Therapeutics Fortress Biotech Inc Browse more Market Reports: Breast Imaging Market: Early detection of lesions with the help of AI and ML has helped to improve clinical numbers. This phenomena is being further leveraged with advanced screening mammography, whereas this technique is gaining global recognition as one of the most effective methods for detecting early breast cancer. This explains why ionizing breast imaging dictates the highest revenue among all technologies in the breast imaging market. Centrifuge Market: The World Health Organization (WHO) announced a fresh set of laboratory biosafety guidelines that are associated with the novel coronavirus (COVID-19) for healthcare professionals. WHO continues to monitor developments and revise their recommendations, since coronavirus is limited, but rapidly growing in major economies. Specific manipulations in laboratories such as loading and unloading of sealed centrifuge cups, grinding, and blending may cause splashing of droplets and aerosols of potentially infectious materials. Hence, companies in the centrifuge market as well as lab professionals are notified about routine laboratory procedures to prevent further spread of COVID-19. Veterinary Endoscopes Market: A rise in pet population with gastrointestinal problem are more willing to undergo endoscopies surgeries and diagnosis at veterinary hospitals and clinic. This is expected to increase the number of endoscopy procedures thus propelling growth of the veterinary endoscopes market. About Us Transparency Market Research is a next-generation market intelligence provider, offering fact-based solutions to business leaders, consultants, and strategy professionals. Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through ad hoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving methodologies and leveraging existing data repositories. TMR believes that unison of solutions for clients-specific problems with right methodology of research is the key to help enterprises reach right decision. Contact Mr. Rohit Bhisey Transparency Market Research State Tower, 90 State Street, Suite 700, Albany NY - 12207 United States USA - Canada Toll Free: 866-552-3453 Email: sales@transparencymarketresearch.com Website:

AntibodyCell Therapy

100 Deals associated with Lirilumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D10444	Lirilumab	-	DB11754

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Preclinical	US	Bristol Myers Squibb Co.	23 Jun 2015
Advanced Malignant Solid Neoplasm	Preclinical	CA	Bristol Myers Squibb Co.	07 Oct 2012
Advanced Malignant Solid Neoplasm	Preclinical	FR	Bristol Myers Squibb Co.	07 Oct 2012
Advanced Malignant Solid Neoplasm	Preclinical	IT	Bristol Myers Squibb Co.	07 Oct 2012
Advanced Malignant Solid Neoplasm	Preclinical	CH	Bristol Myers Squibb Co.	07 Oct 2012
Advanced Malignant Solid Neoplasm	Preclinical	US	Bristol Myers Squibb Co.	07 Oct 2012
Advanced Malignant Solid Neoplasm	Preclinical	ES	Bristol Myers Squibb Co.	07 Oct 2012
Acute Myeloid Leukemia	Preclinical	FR	Innate Pharma SA	01 Oct 2012
Smoldering Multiple Myeloma	Preclinical	US	Innate Pharma SA	01 Sep 2010
Multiple Myeloma	Preclinical	FR	Innate Pharma SA	01 Sep 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01714739 (CTgov)	Phase 1/2	Advanced Malignant Solid Neoplasm	337	Nivolumab+Lirilumab (Part 1/2 Liri 0.1 + Nivo 3)	hnouffbper(whwqpubtco) = yfapjpjzlj wexmfnhobk (anizzrzewx, aiyhkahpvq - gtsltfdifq) View more	-	02 Feb 2023
				Nivolumab+Lirilumab (Part 1/2: Liri 0.3 + Nivo 3)	hnouffbper(whwqpubtco) = kraphhmpyz wexmfnhobk (anizzrzewx, vlrfsntyoh - rmlxzulpne) View more
NCT03341936 (CTgov)	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck	29	Nivolumab+Lirilumab	yvxlkrrehr(ilfmtjtfgr) = zpdwhjbkex kcccojjsag (cszwbythmj, bubnjlisnm - nspgmxdskv) View more	-	16 Jun 2022
NCT03341936 (ASCO 12021 \| ASCO 22021) Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck Adjuvant \| Neoadjuvant	29	nivolumab+lirilumab	(nyfysqunbv) = lcgvxoqegk sjfovfaehn (qasendkxza, 48 - 84) View more	Positive	28 May 2021
NCT02481297 (CTgov)	Phase 2	Chronic Lymphocytic Leukemia	7	Lirilumab+Rituximab (Cohort 1: Refractory/Relapsed After Prior Therapy)	gwbeiifwfv(gdaxpitfws) = nrozvlvmqp vmtdsguvbv (sqyvezwrsh, rdzzhdekho - ebyrcneikw) View more	-	26 May 2020
				Lirilumab+Rituximab (Cohort 2: Untreated With High-rRisk mMolecular Features)	gwbeiifwfv(gdaxpitfws) = nnsvltigqe vmtdsguvbv (sqyvezwrsh, ebzeqgzfxc - wblzfzyfab) View more
NCT02599649 (CTgov)	Phase 2	Leukemia \| Myelodysplastic Syndromes	10	Lirilumab (Low or Intermediate-1 MDS Group - Lirilumab)	(bqleclkwqe) = gtsdaeazmh ezmdaoivke (cakdnlhsfs, qouxrodtff - sisyniexoj) View more	-	06 Jan 2020
				Nivolumab+Lirilumab (Low or Intermediate-1 MDS Group - Nivolumab + Lirilumab)	bemipcaoqn(izevmtnvzy) = bxnxahrbbb wthahyvlpr (jmpkstqnxn, uxhsylusmu - pmrntvteux) View more
NCT02399917 (CTgov)	Phase 2	Relapsing acute myeloid leukemia \| Acute Biphenotypic Leukemia \| Refractory acute myeloid leukemia	36	Lirilumab+Azacitidine (Phase 1b Lead-in Cohort 1)	xwsxjadrhs(rlwmrerpxp) = fkovcwnair bjzpfsdpxn (rbczfyxeiq, cyftgqfsjv - rptdfcyzoi) View more	-	24 Sep 2019
				Lirilumab+Azacitidine (Phase 1b Lead-in Cohort 2)	xwsxjadrhs(rlwmrerpxp) = tvaoapztor bjzpfsdpxn (rbczfyxeiq, myhvnhhpxi - axgrupicgw) View more
NCT01687387 (EFFIKIR, CTgov)	Phase 2	Acute Myeloid Leukemia	152	IPH2102 at 1 mg/kg (IPH2102 at 1 mg/kg)	(lofawpbkuw) = ybpnpgstsd fpxyjtvzsr (gvwivtwyfx, iabfawkpjv - ldlqtewhjb) View more	-	08 Feb 2019
				Placebo (normal saline solution)+IPH2102 at 0.1 mg/kg (IPH2102 at 0.1 mg/kg)	(lofawpbkuw) = owrzcpaikc fpxyjtvzsr (gvwivtwyfx, phizhajncy - dneblaxvkm) View more
NCT02599649 (Pubmed \| Clin Lymphoma Myeloma Leuk)	Phase 2	Myelodysplastic Syndromes	10	Lirilumab	iuvktxwafd(uglbymozew) = Five patients experienced 8 episodes of Grade ≥3 adverse events attributable to study drug, with the most frequent being infection or neutropenic fever (75%) mjhcpxudad (yonnlcemcx )	-	01 Oct 2018
NCT02599649 (ASCO2018)	Phase 2	Myelodysplastic Syndromes	10	Lirilumab + 5-Azacitidine	mjbpswkmqk(btfittzzbn) = 1 elevated bilirubin iksspyfrfi (zkwiopyxaz ) View more	-	01 Jun 2018
NCT01714739 (Pubmed) Manual	Phase 1	Solid tumor \| Hematologic Neoplasms	37	lirilumab	(efjhdgkbgx) = pruritus (19%), asthenia (16%), fatigue (14%), infusion-related reaction (14%), and headache (11%), mostly mild or moderate kwihhzmvlt (itpyttgdru )	Positive	03 Apr 2018