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.

开始日期2024-12-01

申办/合作机构

Hoosier Cancer Research Network

[+3]

NCT06152523 / Not yet recruiting临床2期IIT

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.

开始日期2023-12-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

NCT05903092 / Recruiting临床2期IIT

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.

开始日期2023-09-26

申办/合作机构

Hoosier Cancer Research Network

[+2]

100 项与 Monalizumab 相关的临床结果

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100 项与 Monalizumab 相关的转化医学

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100 项与 Monalizumab 相关的专利（医药）

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项与 Monalizumab 相关的文献（医药）

2024-09-13·Future Oncology

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

Article

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

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).

2024-05-01·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

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

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.

2024-02-01·Journal for immunotherapy of cancer

Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors

Article

作者: Banerjee, Susana ; Cheng, Lin-Yang ; Ascierto, Maria L ; Naidoo, Jarushka ; Carneiro, Benedito A ; Diamond, Jennifer R ; Palmer, Doug C ; Das, Mayukh ; Alonso-Gordoa, Teresa ; Wang, Ding ; Kourtesis, Panagiotis ; Standifer, Nathan E ; Hellmann, Matthew D ; Patel, Sandip P

Background:

The combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors.

Main body:

Immunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0–1, and 1–3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+and granzyme B+cells were observed.

Conclusions:

Although efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME.

Trial registration number:

NCT02671435.

111

项与 Monalizumab 相关的新闻（医药）

2024-11-11

·PRNewswire

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

细胞疗法孤儿药快速通道免疫疗法临床2期

2024-11-08

·Business Wire

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.

免疫疗法临床申请

2024-11-04

·ioncology

ESMO 2024丨多西他赛仍是PD-（L）1抑制剂耐药晚期NSCLC患者的标准治疗

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标” 编者按：抗PD-(L)1已获批用于晚期非小细胞肺癌（NSCLC）的治疗。然而，大多数患者因治疗选择有限在接受抗PD-(L)1治疗期间会出现疾病进展。在2024欧洲肿瘤内科学会（ESMO）年会上，来自法国马赛Pascale Tomasini教授分享了PD-(L)1抑制剂耐药的晚期非小细胞肺癌(NSCLC)患者的精准免疫肿瘤治疗(PIONeeR)：一项靶向确定耐药通路的Ib/IIa期临床试验的研究结果。《肿瘤瞭望》在现场采访了Pascale Tomasin教授，分享主要研究成果以及 PD - (L)1 抑制剂耐药的晚期非小细胞肺癌患者当下的治疗策略、未来展望。这项开放标签、多中心、对照随机研究使用了贝叶斯自适应设计。在序贯或同时接受PD-(L)1和铂类化疗后疾病进展的晚期NSCLC患者符合纳入标准。患者随机为4组，A组：度伐利尤单抗（Du）+ Monalizumab，B组：Du + Oleclumab，C组：Du + Ceralasertib，E组：Du +赛沃替尼或对照组：多西他赛。主要终点是12周疾病控制率（12-w DCR）根据RECIST 1.1。主要次要终点包括缓解持续时间（DoR）、总缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和安全性。中期分析使用了30%的无效边界。如果存在高概率（P ≥ 90%）12-w DCR达到D组的12-w DCR，则认为联合治疗有效。 114例患者被随机分配到A组，n=28；B组，n=3；C组，n=32；D组，n=31；E组，n=20。由于缺乏疗效，B组和E组提前关闭。在D组中，11例患者在接受治疗前退出。有效性层面，对照组的12-w DCR为54.5%（95%CI [34.0%; 74.3%]），A组为24.1% [10.7%; 41.0%]，B组为0%，C组为50% [33.1%; 66.9%]，E组为13.6% [3.0%; 30.4%]；A组和C组的P值分别为1.2%和36.8%。与D组相比，实验组在PFS或OS方面没有显著获益。然而，C组中有5例患者根据RECIST达到了部分缓解（PR），中位DoR为5.6个月[2.1; 9.7]。安全性相当。 PIONeeR 试验是学术合作的成功案例，通过使用创新的自适应设计来识别新型免疫治疗（IO）组合的疗效信号，探索克服晚期 NSCLC 对 PD-(L) 1 抑制剂耐药性的方法。虽然没有实验组正式达到疗效目标，但一些患者从包括 ceralasertib 和 monalizumab 的组合中获得了长期临床益处。目前，综合生物标志物分析正在进行中，以预测受益于这些联合治疗的患者。 01 《肿瘤瞭望》：2024 ESMO发布了一项针对已确定耐药途径的 Ib/IIa 期临床试验结果，请问您如何看待 PD - (L)1 抑制剂耐药的晚期非小细胞肺癌患者的治疗策略?（LBA8） Dr. Pascale Tomasini：多西他赛目前仍是 PD - (L)1 抑制剂耐药的晚期非小细胞肺癌（NSCLC）标准治疗方法，这表明在某些情况下，对于患者的治疗需求还未得到充分满足。在过去的十年里，人们研究了几种不同的方案，试图通过不同的组合来克服对 PD - 1 和 PD - (L)1 抑制剂的耐药性。尽管进行了多种尝试，但到目前为止，还没有一种组合被证明比多西他赛更好。 Dr. Pascale Tomasini: I think there is a real unmet need in these situations, as docetaxel is still the standard-of-care. During the last decade, several different options were studied in order to overcome resistance to PD-1 and PD-L1 inhibitors with several different combinations, but no combination has been shown to be better than docetaxel so far. 02 《肿瘤瞭望》：可供患者参加的临床试验越来越多。加入PD-L1免疫组化检测是否有助于为PD-L1耐药NSCLC患者选择治疗方式？ Dr. Pascale Tomasini: 目前，许多不同的组合正在与其他检查点抑制剂（如 TIGIT 抑制剂、LAG - 3 抑制剂）以及一些靶向疗法进行研发。但我认为仅靠 PD - (L)1 不足以预测这些药物的疗效。因此，我认为需要进行大型生物标志物分析，并整合多种生物标志物，以确定哪些患者可能从这些组合治疗中受益，与仍然是标准治疗方法的多西他赛相比，找到更优的治疗方案。 Dr. Pascale Tomasini: Many different combinations are being tested with other checkpoint inhibitors, TIGIT inhibitors and LAG-3 inhibitors, or even with some targeted therapies. I don’t think PD-(L)1 alone would be enough to predict the efficacy of these drugs. I think there is a need for a large biomarker analysis, and to integrate all these biomarkers to be able to find who among the patients are likely to respond and derive benefit from these combinations as compared to docetaxel, which is still the standard. 03 《肿瘤瞭望》：您能否谈谈PD-L1抑制剂耐药NSCLC领域未满足的需求？ Dr. Pascale Tomasini: 对于晚期非小细胞肺癌且对 PD - 1 和 PD - (L)1 抑制剂耐药的患者来说，目前除了多西他赛之外没有其他更好的选择。这些患者迫切需要找到毒性更小、疗效更好的治疗方法。许多新的治疗选择正在被开发，我希望通过这些治疗选择及进行许多生物标志物分析，能够改善这些患者的治疗策略。 Dr. Pascale Tomasini: Again, there is nothing else other than docetaxel for now in this setting of patients with advanced non-small cell lung cancer resistant to PD-1 and PD-L1 inhibitors. There is a real need for these patients to find something else with less toxicity and better efficacy. Many options are being tested, and I hope with these options and many biomarker analyses, we will be able to improve the strategy for these patients. （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果ASCO会议

100 项与 Monalizumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Monalizumab	-	DB12824

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
局部晚期非小细胞肺癌	临床3期	美国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	中国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	日本	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	澳大利亚	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	巴西	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	加拿大	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	哥伦比亚	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	法国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	德国	AstraZeneca PLC	2022-02-07
局部晚期非小细胞肺癌	临床3期	意大利	AstraZeneca PLC	2022-02-07

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


WCLC2024	临床2期	广泛期小细胞肺癌一线 NKG2A/CD94 \| HLA-E	6	Platinum-based chemotherapy + Durvalumab + Monalizumab	鬱願願衊糧築遞顧襯鏇(鑰築夢鹽構鹹鹹糧醖鑰) = 艱窪齋醖獵膚網廠遞製壓獵選製膚鹹齋鹹窪餘 (簾糧範構醖觸鏇鏇淵壓 )	积极	2024-09-08
NCT03822351 (COAST, ASCO2024) 人工标引	临床2期	不可切除的非小细胞肺癌	189	durvalumab	構鏇築齋鏇範糧顧憲壓(構窪糧願襯蓋製壓簾構) = 鑰蓋糧鹽繭廠顧醖餘鹽淵築糧鹽衊蓋鹽網襯鹹 (鏇範築顧蓋範廠餘淵淵, 14.3 ~ 35.9) 更多	积极	2024-05-24
				durvalumab+oleclumab	構鏇築齋鏇範糧顧憲壓(構窪糧願襯蓋製壓簾構) = 糧鏇繭顧範餘觸餘鬱顧淵築糧鹽衊蓋鹽網襯鹹 (鏇範築顧蓋範廠餘淵淵, 23.1 ~ 48.4) 更多
NCT03088059 (UPSTREAM, ESMO2023)	临床2期	头颈部鳞状细胞癌	66	Durvalumab + Monalizumab	壓獵選顧構夢襯糧遞憲(範顧齋鑰夢廠鬱醖蓋願) = 遞齋艱鏇艱願齋網積膚廠夢網蓋廠積顧繭蓋願 (憲夢餘遞繭鑰廠網鬱壓 ) 更多	不佳	2023-10-22
				monalizumab (Physician's choice)	壓獵選顧構夢襯糧遞憲(範顧齋鑰夢廠鬱醖蓋願) = 廠範憲築鬱糧積蓋糧範廠夢網蓋廠積顧繭蓋願 (憲夢餘遞繭鑰廠網鬱壓 ) 更多
NCT04590963 (INTERLINK-1, Corporate Publications) 人工标引	临床3期	复发性头颈部鳞状细胞癌	600	Cetuximab+Monalizumab	齋製積顧鏇鹹遞襯鹹憲(觸鏇繭簾廠衊襯蓋範壓) = not reach 積糧製鏇鹽襯艱範觸廠 (蓋願襯衊觸鬱顧鏇製積 )	不佳	2022-08-01
				Cetuximab+Placebo
NCT03794544 (AACR2022) 人工标引	临床2期	非小细胞肺癌新辅助	84	Durvalumab	網顧願鬱艱壓顧築網淵(鏇遞製餘糧夢範鏇蓋鏇) = 製襯齋選簾壓鏇鏇鑰觸鬱壓鹽夢窪獵壓壓鬱壓 (獵淵範餘窪遞夢願廠鬱, 2.4 ~ 29.2) 更多	积极	2022-06-15
				Durvalumab+Oleclumab	網顧願鬱艱壓顧築網淵(鏇遞製餘糧夢範鏇蓋鏇) = 鹽願襯艱齋構選鹽醖鏇鬱壓鹽夢窪獵壓壓鬱壓 (獵淵範餘窪遞夢願廠鬱, 5.4 ~ 41.9) 更多
NCT03822351 (COAST, Pubmed \| J Urol)	临床2期	非小细胞肺癌 III期巩固	189	Durvalumab	願餘壓艱憲窪艱繭淵鬱(鑰蓋積鹹網艱衊製網積) = 夢醖糧窪夢選鏇網積獵夢齋襯範夢鹹夢願鹹鬱 (築鏇艱選壓蓋衊遞餘鬱, 9.6 ~ 29.2)	积极	2022-04-22
				Durvalumab+Oleclumab	願餘壓艱憲窪艱繭淵鬱(鑰蓋積鹹網艱衊製網積) = 積製廠範積蓋繭壓鑰窪夢齋襯範夢鹹夢願鹹鬱 (築鏇艱選壓蓋衊遞餘鬱, 18.8 ~ 43.2)
NCT02643550 (ESMO_IO2021) 人工标引	临床2期	复发性头颈部鳞状细胞癌一线	40	durvalumab+Monalizumab+cetuximab	餘糧窪觸淵簾鹹壓網繭(範壓蓋蓋膚夢築夢範壓) = 淵艱壓壓夢製觸鏇膚積膚選憲繭淵醖膚築醖窪 (窪襯願遞構構鹽膚艱鹽, 20 ~ 48) 更多	积极	2021-12-09
NCT03088059 (UPSTREAM, Pubmed \| Eur J Cancer Care (Engl)) 人工标引	临床2期	头颈部鳞状细胞癌	26	Monalizumab	糧糧選獵糧願獵壓鬱膚(夢窪願鏇鑰顧鏇淵醖製) = 鹽憲選觸築願醖衊淵鹽網廠糧蓋積鹹糧廠積壓 (繭積繭選積糧積蓋醖遞 ) 更多	不佳	2021-10-09
NCT02643550 (ASCO2020) 人工标引	临床2期	头颈癌转移	40	cetuximab+monalizumab	鏇齋憲憲壓襯糧選觸遞(鬱廠顧積鹹遞鹽糧範願) = 餘淵醖蓋鹽壓獵鬱窪憲艱淵觸構選糧憲鏇積繭 (憲遞願餘鏇壓憲襯簾鹹, 11 ~ 35) 更多	积极	2020-05-29
NCT02671435 (ASCO_GI2020) 人工标引	临床1/2期	转移性微卫星稳定结直肠癌一线 Microsatellite Stable (MSS)	35	bevacizumab+chemotherapy+monalizumab+durvalumab (DMCB)	築願窪鹹醖餘簾範願遞(糧膚觸繭網鏇繭鏇繭醖) = 選遞醖積餘鑰範範鬱選繭鬱鑰蓋製淵糧夢膚膚 (膚鏇顧艱範鏇獵壓艱積 ) 更多	积极	2020-01-25
				cetuximab+chemotherapy+monalizumab+durvalumab (DMCC)	築願窪鹹醖餘簾範願遞(糧膚觸繭網鏇繭鏇繭醖) = 窪簾艱選鹹艱遞觸壓築繭鬱鑰蓋製淵糧夢膚膚 (膚鏇顧艱範鏇獵壓艱積 ) 更多