ENHANCE (Elevated NKG2A and HLA-E Amplify NK/CD8 Checkpoint Engagers): A Phase 2 Trial of Durvalumab (MEDI4736) Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer

This is a phase 2 open-label two cohort study of durvalumab plus monalizumab in patients with BCG-unresponsive or exposed CIS NMIBC. Arm A will enroll 43 participants who have cancer in situ (CIS) with or without high grade papillary urothelial cancer. Arm B will enroll 17 participants who do not have cancer in situ (CIS) but do have high grade papillary urothelial cancer. Eligible patients will be enrolled to receive up to 13 cycles of monthly combination of monalizumab and durvalumab. Both monalizumab and durvalumab will be administered intravenously (IV) every 28 days.

Start Date01 Dec 2024

Sponsor / Collaborator

Hoosier Cancer Research Network

[+3]

NCT06152523 / Not yet recruitingPhase 2IIT

Monalizumab and MEDI5752 in Patients With MSI and/or dMMR Metastatic Cancer

MSI is a molecular indicator of defective DNA mismatch repair (dMMR). The MSI/dMMR status is observed in all tumor types, representing notably 5% of metastatic colorectal cancers (mCRC), 25% of advanced endometrial cancer and 8% of metastatic gastric cancer.
MSI/dMMR cancers are highly immunogenic. MSI/dMMR tumors are characterized by a high tumor mutational burden with highly immunogenic neoantigens. These tumors are associated with an upregulation of immune checkpoints (PD1, PDL1, CTLA4, etc.) that protects MSI cancer cells from their hostile immune micro-environment, characterized by a high infiltration of activated cytotoxic T CD8+ and NK lymphocytes. Consequently, MSI/dMMR cancers are highly sensitive to ICIs, whatever the tumor location. MSI/dMMR status is a predictive biomarker for the efficacy of immunotherapy, regardless of the tumor type. Then, by several phase II and III studies The efficacy of immunotherapy has been demonstrated as front-line treatment for patients with chemotherapy-naive MSI/dMMR mCRC and gastric cancer. The phase III KEYNOTE-177 trial evaluating first-line treatment of pembrolizumab in patients with MSI/dMMR mCRC demonstrated its superiority over first-line chemotherapy, with a significant improvement of health-related quality of life. At final analysis, the median follow-up was 44.5 months. Median PFS was 16.5 versus 8.2 months (HR = 0.59; 95%CI 0.45-0.79). The hazard ratio favored pembrolizumab versus chemotherapy with a trend toward reduction in the risk of death (HR 0.74; 95% CI, 0.53-1.03; P=0.0359), despite a 60% effective crossover rate. Pembrolizumab has been approved by the FDA and the EMA for patients with newly diagnosed MSI/dMMR mCRC and is now the standard of care for this population. Also, the phase III CHECKMATE-649 trial reveal that the Combination of immunotherapy and cytotoxic chemotherapy is the new standard of care for patients with newly diagnosed metastatic oesogastric cancer. Importantly, results of the CHECKMATE-649 are outstanding for the subgroup population of MSI/dMMR gastric cancer patients (N = 44). Indeed, the unstratified hazard ratio for OS with nivolumab plus chemotherapy versus chemotherapy alone was 0.33 (95% CI 0.12-0.87) for patients with MSI/dMMR tumors. All in all, ICIs are the standard of care in first-line setting for patients with mCRC or metastatic oesogastric cancer. Besides, several phase II studies suggest that ICI combinations might overcome primary resistance to anti-PD1 monotherapy These data justify the development of bispecific monoclonal antibodies targeting both PD1 and CTLA4 such as MEDI5752. MEDI5752 has been developed based on the observation that there is a higher expression of PD-1/CTLA-4 on tumor resident versus peripheral T cells. Preclinical data show MEDI5752 fully suppresses PD-1 and preferentially inhibits CTLA-4 in the tumor versus the periphery, which is meant to uncouple CTLA-4 dependant peripheral toxicity from antitumor activity Natural killer cells are integral to the functioning of the innate immune system and play an important role in innate antitumor immunity. There is a growing body of evidence for targeting the NKG2A/HLA-E axis in combination with other ICIs to sensitize tumors to ICI therapy. NKG2A recognizes the non-classical HLA class I molecule HLA-E. The NKG2A receptor is found on peripheral NK cells and subsets of T cells in cancer patients. It is also present in tumor-infiltrating NK and cytotoxic T cells. Importantly, NK cells and the NKG2A/HLA-E axis play a crucial role in MSI/dMMR tumors. Therefore, a combined blockade of non-redundant checkpoint pathways to unleash NK and T cells seems particularly promising for MSI/dMMR neoplasms. Monalizumab specifically binds and blocks the inhibitory receptor NKG2A. Monalizumab has been investigated in combination with ibrutinib (in chronic lymphoid leukemia), cetuximab +/- durvalumab (in squamous cell carcinoma of the head and neck, and in solid tumors), durvalumab +/- FOLFOX (in solid tumors). In the first-in-human dose escalation of monalizumab plus durvalumab, a manageable toxicity profile was shown.
Taken together, these data provide a strong rational to combine an inhibitor of the NKG2A/HLA-E axis with a bispecific monoclonal antibody targeting both PD1 and CTLA4 for patients with metastatic MSI/dMMR cancers.

Start Date01 Dec 2023

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT05903092 / RecruitingPhase 2IIT

A Phase II Trial of MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer (MOZART)

The study treatment will consist of a platinum drug (carboplatin or cisplatin per investigator's choice) plus etoposide plus durvalumab plus monalizumab every 3 weeks for 4 cycles. After 4 cycles, subjects will continue maintenance treatment with durvalumab plus monalizumab every 4 weeks until disease progression, unacceptable toxicity, decision to stop study treatment, or withdrawal of consent. Patients who have received one prior cycle of treatment before enrolling on the study will receive a total of 4 cycles with monalizumab, durvalumab, and chemotherapy. There will be a safety lead-in phase, including 6 to 12 patients, to confirm the safety of the proposed dose of monalizumab to use in combination with chemotherapy and durvalumab.

Start Date26 Sep 2023

Sponsor / Collaborator

Hoosier Cancer Research Network

[+2]

100 Clinical Results associated with Monalizumab

100 Translational Medicine associated with Monalizumab

100 Patents (Medical) associated with Monalizumab

Literatures (Medical) associated with Monalizumab

13 Sep 2024·Future Oncology

PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer

Article

Author: Barlesi, Fabrice ; Mann, Helen ; Newton, Michael ; Zimmer Gelatti, Ana Caroline ; Goldberg, Sarah B ; Cho, Byoung Chul ; Yoh, Kiyotaka ; Gopinathan, Aarthi ; Bielecka, Zofia Felicja ; Aggarwal, Charu

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov).

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.

01 May 2024·Combinatorial Chemistry & High Throughput Screening

A Novel Natural Killer Cell-related Gene Signature for Improving the Prediction of Prognosis and Immunotherapy Response in Bladder Cancer

Article

Author: Wei, Xifeng ; Ma, Xudong ; Li, Shuai ; Liu, Ranlu ; Yang, Guanghua

Background:Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA.Methods:We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment.Results:We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells.Conclusion:To sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.

News (Medical) associated with Monalizumab

11 Nov 2024

·www.prnewswire.com

NK Cell Therapy Clinical Trial Pipeline Appears Robust With 140+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

NK cell therapy is gaining momentum as a promising solution to unmet medical needs in cancer treatment, offering safer, targeted options for patients unresponsive to traditional therapies. Increased R&D investment, regulatory support, and successful clinical trials have bolstered confidence in these therapies, while technological advances in cell production are set to meet growing demand. Rising cancer rates and heightened public awareness further amplify market potential, making NK cell therapy a pivotal area of growth in oncology. LAS VEGAS, Nov. 11, 2024 /PRNewswire/ -- DelveInsight's ' NK Cell Therapy Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline NK cell therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the NK cell therapy pipeline domain. Key Takeaways from the NK Cell Therapy Pipeline Report DelveInsight's NK cell therapy pipeline report depicts a robust space with 140+ active players working to develop 160+ pipeline NK cell therapies. Key NK cell therapy companies such as Amgen, Innate Pharma, Nektar Therapeutics, SMT bio Co., Ltd., Alphageneron Pharmaceuticals, XNK Therapeutics, ImmunityBio, Cellid, Cantargia, Affimed Therapeutics, Takeda, Artiva Biotherapeutics, Sanofi, Dragonfly Therapeutics, INmune Bio, NKGen Biotech, Asclepius Technology Company Group, Glycostem Therapeutics (IPD Therapeutic), Wugen, Celularity, VERAXA, GamidaCell, MiNK Therapeutics, Indapta Therapeutics, ImmunityBio, Inc., Allife Medical Science and Technology, Nkarta, Base Therapeutics, GT Biopharma, Athenex, Ambicion, Biohaven Pharmaceuticals, Acepodia, Bright Path Biotherapeutics, Nkarta Therapeutics, Qihan Biotech, Century Therapeutics, Fate Therapeutics, Chimeric Therapeutics, Senti Biosciences, GICELL, Deverra Therapeutics, Medigen Biotechnology Corporation, GlaxoSmithKline, CytoImmune Therapeutics, Nuwacell Biotechnologies Co., Ltd., and others are evaluating new NK cell therapies to improve the treatment landscape. Promising NK cell therapies in the pipeline such as Bemarituzumab, Monalizumab, NKTR-225, SMT-NK, Enkastim, CellProtect, ALT 803, BVAC-C, PD-L1.t-haNK, Nidanilimab, M ceNK, HER2 t-haNK, AFM-13, TAK-007, IPH4102, AB-101, KDS-1001, AB-201, DF9001, INKmune, IPH65, SNK01, IPH6101 (SAR443579), BCMA CAR-NK 92 cells, DF1001, Allogeneic Natural Killer Cell Therapy (oNKord), WU-NK-101, AFM24, CYNK-001, FLYSYN, GDA-201, AGENT-797, CYNK-101, SAR445514, IDP-023, DF6002, CD19.taNK, Anti-PSMA CAR NK cells, DF2001, NKX101, NK510, GTB-3550, KUR-501, RK-pulsed autologous antigen-presenting cells (APCs), BHV-1100, ACE1702, iPS NKT, Anti-CD19/CD22 CAR NK cell therapy, NKX019, KUR-502, BVAC-P, QN-019a, QN-030a, QN-023a, CNTY-101, FT576, CHM 0201, SENTI-202, AFM28, DF8001, FT522, SNK02, GIC-102, DVX201, Magicell®-NK, GSK4381562, CYTO NK-102, NCR300, and others are under different phases of NK cell therapy clinical trials. In October 2024, Immunitybio announced that the first patients had been dosed in an initial trial studying the potential of the company's CAR-NK cell therapy targeting CD-19 in the treatment of non-Hodgkin's lymphoma (NHL). In July 2024, The U.S. Food and Drug Administration (FDA) gave Nkarta the green light to launch a clinical trial testing its cell therapy candidate NKX019 in people with ANCA-associated vasculitis (AAV) and other autoimmune disorders. In May 2024, KGen Biotech announced that its Safety Review Committee had cleared the Company's cryopreserved autologous, expanded, and enhanced SNK01 to progress into Phase II clinical development. In May 2024, Fate Therapeutics announced that a late-breaking abstract featuring preclinical data from its FT522 program for autoimmune diseases will be featured at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. In April 2024, Sanofi moved its natural killer (NK) cell engager candidate SAR443579/IPH6101 to a Phase II trial evaluating the drug's use in treating a range of blood cancers. In April 2024, the FDA granted orphan drug designation to the investigational therapy IGNK001 (Gengleucel) for patients with acute myeloid leukemia (AML). In February 2024, Indapta Therapeutics received FDA Fast Track Designation for its natural killer (NK) cell therapy IDP-023 for patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Request a sample and discover the recent advances in the NK cell therapy segment @ NK Cell Therapy Pipeline Report The NK cell therapy pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage NK cell therapies, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the NK cell therapy clinical trial landscape. NK Cell Therapy Overview Natural Killer (NK) cell therapy is an innovative approach in immunotherapy that harnesses the power of NK cells, a vital component of the innate immune system. Unlike T cells, which require prior sensitization to target cancer cells, NK cells can recognize and kill abnormal cells without prior exposure. This unique ability makes NK cell therapy a promising option for treating various cancers, including hematologic malignancies like leukemia and lymphoma, as well as solid tumors. By isolating and activating NK cells from a patient's blood or using engineered NK cells from healthy donors, researchers aim to enhance the immune response against tumors, leading to improved patient outcomes. Recent advancements in genetic engineering, such as the introduction of chimeric antigen receptors (CAR) into NK cells, are further enhancing their specificity and efficacy against cancer cells. The clinical applications of NK cell therapy are expanding rapidly, supported by a growing body of research and early-phase clinical trials. These studies have shown promising results, demonstrating the ability of NK cell therapy to induce durable remissions in patients with refractory cancers. Furthermore, the off-the-shelf nature of certain NK cell therapies allows for quicker treatment deployment compared to traditional CAR-T cell therapies, which require a personalized approach. Challenges remain, including optimizing NK cell expansion, persistence, and overcoming the immunosuppressive tumor microenvironment. However, ongoing research into combination therapies, such as pairing NK cell therapy with checkpoint inhibitors or monoclonal antibodies, is expected to enhance the therapeutic potential of NK cells and provide new hope for cancer patients. Find out more about NK cell therapy @ Novel NK Cell Therapies A snapshot of the Pipeline NK Cell Therapies mentioned in the report: Learn more about the emerging NK cell therapies @ NK Cell Therapy Clinical Trials NK Cell Therapy Therapeutics Assessment The NK cell therapy pipeline report proffers an integral view of the emerging NK cell therapies segmented by stage, product type, molecule type, and route of administration. Scope of the NK Cell Therapy Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Vaccines, Monoclonal antibody, Peptides, Polymer, Small molecule Key NK Cell Therapy Companies: Amgen, Innate Pharma, Nektar Therapeutics, SMT bio Co., Ltd., Alphageneron Pharmaceuticals, XNK Therapeutics, ImmunityBio, Cellid, Cantargia, Affimed Therapeutics, Takeda, Artiva Biotherapeutics, Sanofi, Dragonfly Therapeutics, INmune Bio, NKGen Biotech, Asclepius Technology Company Group, Glycostem Therapeutics (IPD Therapeutic), Wugen, Celularity, VERAXA, GamidaCell, MiNK Therapeutics, Indapta Therapeutics, ImmunityBio, Inc., Allife Medical Science and Technology, Nkarta, Base Therapeutics, GT Biopharma, Athenex, Ambicion, Biohaven Pharmaceuticals, Acepodia, Bright Path Biotherapeutics, Nkarta Therapeutics, Qihan Biotech, Century Therapeutics, Fate Therapeutics, Chimeric Therapeutics, Senti Biosciences, GICELL, Deverra Therapeutics, Medigen Biotechnology Corporation, GlaxoSmithKline, CytoImmune Therapeutics, Nuwacell Biotechnologies Co., Ltd., and others. Key Pipeline NK Cell Therapies: Bemarituzumab, Monalizumab, NKTR-225, SMT-NK, Enkastim, CellProtect, ALT 803, BVAC-C, PD-L1.t-haNK, Nidanilimab, M ceNK, HER2 t-haNK, AFM-13, TAK-007, IPH4102, AB-101, KDS-1001, AB-201, DF9001, INKmune, IPH65, SNK01, IPH6101 (SAR443579), BCMA CAR-NK 92 cells, DF1001, Allogeneic Natural Killer Cell Therapy (oNKord), WU-NK-101, AFM24, CYNK-001, FLYSYN, GDA-201, AGENT-797, CYNK-101, SAR445514, IDP-023, DF6002, CD19.taNK, Anti-PSMA CAR NK cells, DF2001, NKX101, NK510, GTB-3550, KUR-501, RK-pulsed autologous antigen-presenting cells (APCs), BHV-1100, ACE1702, iPS NKT, Anti-CD19/CD22 CAR NK cell therapy, NKX019, KUR-502, BVAC-P, QN-019a, QN-030a, QN-023a, CNTY-101, FT576, CHM 0201, SENTI-202, AFM28, DF8001, FT522, SNK02, GIC-102, DVX201, Magicell®-NK, GSK4381562, CYTO NK-102, NCR300, and others. Dive deep into rich insights for new NK cell therapies, visit @ NK Cell Therapy Drugs Table of Contents For further information on the NK cell therapy pipeline therapeutics, reach out @ NK Cell Therapy Treatment Drugs Related Reports NK Cell Therapy Market NK Cell Therapy Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key NK cell therapy companies including Sanofi, Dragonfly Therapeutics, INmune Bio, NKGen Biotech, Asclepius Technology Company Group, Glycostem Therapeutics (IPD Therapeutic), Wugen, Celularity, VERAXA, GamidaCell, MiNK Therapeutics, Indapta Therapeutics, among others. Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies, including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Cell TherapyOrphan DrugFast TrackImmunotherapyPhase 2

08 Nov 2024

·www.businesswire.com

Innate Pharma Highlights Data From Its Innovative Oncology Portfolio Selected for the SITC Annual Meeting 2024

MARSEILLE, France--( BUSINESS WIRE )--Regulatory News: Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“ Innate ” or the “ Company ”) today announced that new preclinical data supporting the clinical development of its proprietary next generation antibody-drug conjugate ( ADC) and innovative tetra-specific ANKET ® will be presented at the SITC Annual Meeting 2024. “We are thrilled to share our latest preclinical data at the SITC Annual Meeting, highlighting the potential of IPH6501, our tetra-specific NK cell engager and IPH4502, our innovative ADC targeting Nectin-4. These findings underscore our commitment to advancing next-generation immunotherapies and reflect significant progress in the development of our drug candidates. We look forward to engaging with the scientific community as we continue to push the boundaries of next generation immunotherapies,” commented Pr. Eric Vivier, Chief Scientific Officer of Innate Pharma. Details of the presentations Society for Immunotherapy of Cancer (SITC) 39 th Annual Meeting | 6-10 November, Houston, Texas and Virtual Harnessing NK Cells in Cancer Therapies Session 107d: NK Cells and Innate Immunity Presentation Type: Oral Presentation Session Date and Time: Friday, Nov. 8, 2024, 3:50-5:25pm CST Presentation Time: 4:35pm CST Speaker: Eric Vivier, Chief Scientific Officer, Innate Pharma (co-chair of the session) Preclinical Characterization of IPH6501: A Novel IL2v-Armed Tetraspecific NK Cell Engager Targeting CD20 in Relapsed or Refractory B cell Non-Hodgkin Lymphoma Subtypes and Post-CAR-T Therapy. Abstract Number: 1083 Presentation Type: Poster Presentation Primary Category: Immuno-Conjugates and Chimeric Molecules Poster Presentation Day : Friday, Nov. 8, 2024 IPH45, a next-generation antibody-drug conjugate (ADC) targeting Nectin-4 Abstract Number: 1056 Presentation Type: Poster Presentation Primary Category: Immuno-Conjugates and Chimeric Molecules Poster Presentation Day: Saturday, Nov. 9, 2024 More information can be found on the JITC website . Protein & Antibody Engineering Summit (PEGS) Europe | November 5-7, Barcelona, Spain and virtual In addition, the presentation entitled « A Next-Generation ADC for Nectin-4 Expressing Tumours: Preclinical Characterisation of IPH45, a Novel and Differentiated Exatecan-Based ADC Targeting Nectin-4 » was presented at the PEGS Europe Summit. The presentation is available on the Company website, in the publications section . About IPH4502 IPH4502 is a novel topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4. Nectin-4 is a cell membrane adhesion protein overexpressed in several solid tumors, including urothelial, breast, lung, ovarian, and pancreatic cancers, with limited expression in normal tissues. In non-clinical models, IPH4502 is well tolerated and shows anti-tumor efficacy in vitro and in vivo . In September 2024, the U.S Food and Drug Administration cleared Innate’s investigational new drug (IND) application to initiate a Phase 1 clinical study of IPH4502 in Nectin-4 expressing solid tumor indications. About IPH6501 IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not a subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA 2023). IPH6501 is currently being evaluated in a Phase 1/2 multicenter trial (NCT06088654), investigating the safety and tolerability of IPH6501 in patients with Relapsed and/or Refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through three therapeutic approaches: monoclonal antibodies, multi-specific NK Cell Engagers via its ANKET ® (Antibody-based NK cell Engager Therapeutics) proprietary platform and Antibody Drug Conjugates (ADC). Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non-small cell lung cancer, several ANKET ® drug candidates to address multiple tumor types as well as IPH4502 a differentiated ADC in development in solid tumors. Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at www.innate-pharma.com and follow us on LinkedIn and X . Information about Innate Pharma shares ISIN code Ticker code LEI FR0010331421 Euronext: IPH Nasdaq: IPHA 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors This press release contains certain forward-looking statements, including those within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. The use of certain words, including “anticipate,” “believe,” “can,” “could,” “estimate,” “expect,” “may,” “might,” “potential,” “expect” “should,” “will,” or the negative of these and similar expressions, is intended to identify forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Company’s reliance on third parties to manufacture its product candidates, the Company’s commercialization efforts and the Company’s continued ability to raise capital to fund its development. For an additional discussion of risks and uncertainties, which could cause the Company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website http://www.amf-france.org or on Innate Pharma’s website, and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2023, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public by the Company. References to the Company’s website and the AMF website are included for information only and the content contained therein, or that can be accessed through them, are not incorporated by reference into, and do not constitute a part of, this press release. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by the Company or any other person that the Company will achieve its objectives and plans in any specified time frame or at all. The Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

ImmunotherapyIND

23 Sep 2024

·pipelinereview.com

Innate Pharma Announces FDA Clearance of the IND for IPH4502, a Nectin-4 ADC to Be Developed in Solid Tumors

MARSEILLE, France I September 23, 2024 I Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“ Innate ” or the “ Company ”) today announced that the U.S Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to initiate a Phase 1 clinical study of IPH4502, its novel and differentiated topoisomerase I inhibitor antibody drug conjugate (ADC) targeting Nectin-4 in solid tumors. Innate expects to initiate the Phase 1 study in the coming months. The Phase 1, open-label, multi-center study, includes a Part 1 Dose Escalation and a Part 2 Dose Optimization, and will assess the safety, tolerability, and preliminary efficacy of IPH4502 as a single agent in advanced solid tumors known to express Nectin-4, including but not limited to urothelial carcinoma, non-small cell lung, breast, ovarian, gastric and colorectal cancers. “ We are thrilled to advance the IPH4502 program, and the IND application acceptance is an important milestone for Innate, as this is our first ADC program to enter the clinic ,” said Dr Sonia Quaratino, Chief Medical Officer of Innate Pharma . “ IPH4502 is a novel and differentiated Nectin-4 ADC that has the potential to provide a new therapeutic option for patients with a cancer expressing a wide range of Nectin-4. Through this Phase 1 study we aim to advance the research on our ADC technology for the benefit of patients. ” About IPH4502 IPH4502 is a novel topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4. Nectin-4 is a cell membrane adhesion protein overexpressed in several solid tumors, including urothelial, breast, esophageal, lung, ovarian, and pancreatic cancers, with limited expression in normal tissues. In non-clinical models, IPH45 was well tolerated and shows anti-tumor efficacy in vitro and in vivo . About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic antibodies and its ANKET ® ( A ntibody-based NK cell E ngager T herapeutics) proprietary platform. Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non-small cell lung cancer, as well as ANKET ® multi-specific NK cell engagers to address multiple tumor types. Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at www.innate-pharma.com and follow us on Twitter and LinkedIn . SOURCE: Innate Pharma

ImmunotherapyINDPhase 1

100 Deals associated with Monalizumab

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KEGG	Wiki	ATC	Drug Bank
-	Monalizumab	-	DB12824

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	TW	AstraZeneca PLC	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	PT	AstraZeneca PLC	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	PH	Innate Pharma SA	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	ES	AstraZeneca PLC	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	GR	Innate Pharma SA	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	PL	Innate Pharma SA	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	IT	Innate Pharma SA	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	BG	AstraZeneca PLC	02 Oct 2020
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Phase 3	FR	Innate Pharma SA	02 Oct 2020
Squamous Cell Carcinoma of Head and Neck	Preclinical	US	AstraZeneca PLC	02 Oct 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03822351 (COAST, CTgov)	Phase 2	Non-small cell lung cancer stage III \| Locally Advanced Lung Non-Small Cell Carcinoma	189	Durvalumab (Control Arm (Durvalumab Monotherapy))	tfestfnnuh(jfffbxdntx) = zbwadhibnd rjcfhogrms (faafmxbrch, jzivegsnpw - bfejpynsys) View more	-	08 Oct 2024
				Monalizumab+Durvalumab (Arm B (Durvalumab + Monalizumab))	tfestfnnuh(jfffbxdntx) = xolwaueqse rjcfhogrms (faafmxbrch, txsvkobrjz - yekbcdniqm) View more
NCT03833440 (PIONeeR, ESMO2024) Manual	Phase 2	Non-Small Cell Lung Cancer Second line \| Third line	114	Durvalumab + Monalizumab (Arm A)	(yovmzwwryd) = sgwhnitiin jasthjskdi (hicnfyfxwz, 10.7 - 41.0)	Negative	26 Sep 2024
				Durvalumab + Oleclumab (Arm B)	(yovmzwwryd) = dkbepvgyxt jasthjskdi (hicnfyfxwz )
WCLC2024	Phase 2	Extensive stage Small Cell Lung Cancer First line NKG2A/CD94 \| HLA-E	6	Platinum-based chemotherapy + Durvalumab + Monalizumab	(tvuxmoitgn) = hlxyuvyplz lgefatkslz (qtqkbuwjda )	Positive	08 Sep 2024
NCT03822351 (COAST, ASCO2024) Manual	Phase 2	Unresectable Lung Non-Small Cell Carcinoma	189	durvalumab	(raippywhjh) = gutoyaydpb ishwkwaepg (ojekykunmw, 14.3 - 35.9) View more	Positive	24 May 2024
				durvalumab+oleclumab	(raippywhjh) = wcpbymjnap ishwkwaepg (ojekykunmw, 23.1 - 48.4) View more
NCT03088059 (UPSTREAM, ESMO2023)	Phase 2	Squamous Cell Carcinoma of Head and Neck	66	Durvalumab + Monalizumab	(losoxzowpa) = atramlkbdq yjbcuzxvts (diojaksuil ) View more	Negative	22 Oct 2023
				monalizumab (Physician's choice)	(losoxzowpa) = sanbutbaes yjbcuzxvts (diojaksuil ) View more
NCT03794544 (NeoCOAST, ESMO2022)	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	(sznvxspchs) = ooxutektun kylfpbclns (riuflilsxk )	-	12 Sep 2022
				Durvalumab + Oleclumab	(sznvxspchs) = gmdromuzne kylfpbclns (riuflilsxk )
NCT04590963 (INTERLINK-1, Corporate Publications) Manual	Phase 3	Recurrent Squamous Cell Carcinoma of the Head and Neck	600	Cetuximab+Monalizumab	(mumzndjsit) = not reach rvodtvuupu (rbsgcxtojj )	Negative	01 Aug 2022
				Cetuximab+Placebo
NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	(zsmlprlsqd) = gpvavmfpwh ahwjywrbbx (kfskomzliy, 2.4 - 29.2) View more	Positive	15 Jun 2022
				Durvalumab+Oleclumab	(zsmlprlsqd) = mzfgrdxiis ahwjywrbbx (kfskomzliy, 5.4 - 41.9) View more
NCT03822351 (COAST, Pubmed \| J Urol)	Phase 2	Non-small cell lung cancer stage III Consolidation	189	Durvalumab	(rplilshuvp) = yyhecxjhqy bexzruocct (xmxhzjppwp, 9.6 - 29.2)	Positive	22 Apr 2022
				Durvalumab+Oleclumab	(rplilshuvp) = dzfceyrgin bexzruocct (xmxhzjppwp, 18.8 - 43.2)
NCT03794544 (NeoCOAST, CTgov)	Phase 2	Non-small cell lung cancer stage IIIA	84	Durvalumab (Durvalumab 1500 mg)	booehpygzs(exmczkttnp) = hkmxpsjnjl hcfgiuzpoh (cjnlfttpxl, exsxwcqyee - nnzfvccpjn) View more	-	24 Feb 2022
				Durvalumab+Oleclumab (Durvalumab 1500 mg + Oleclumab 3000 mg)	booehpygzs(exmczkttnp) = hkyencicjl hcfgiuzpoh (cjnlfttpxl, ivplzvlfzq - detaxxxvjb) View more

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