Ox40 Antibody Clinical Trial

Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. It's immunotherapy treatment, not an alternative treatments. Announces Initiation of Phase 1 Clinical Trial of SL-279252 (PD1/OX40L). An agonistic, humanized monoclonal antibody against receptor OX40 (CD134), with potential immunostimulatory activity. The antibody was well tolerated with minimal toxicity and observation of some tumor size reduction, although none of the patients showed an objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Recently, Phase I monotherapy studies [NCT01644968] have been conducted with an OX40 agonist (9B12, mouse monoclonal anti-OX40 antibody) in patients with metastatic solid tumors. Overall, 81% of the patients were still alive at the six-month mark, and 71% at the nine-month mark. The clinical trials on this list are studying Anti-OX40 Monoclonal Antibody. Strategies for Bispecific Single Chain Antibody in Cancer Immunotherapy. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. One of the goals of the planned clinical trial is to assess the safety of the combination. AU - Grimaldi, Antonio M. Brown , Kevin R. Administration of the CD28 superagonistic antibody JJ316 is an efficient means to treat autoimmune diseases in rats, but the humanized antibody TGN1412 caused devastating side effects in healthy volunteers during a clinical trial. Mori L, Iselin S, De Libero G, and Lesslauer W. 0 mg kg) in healthy volunteers (HVs). com AFM11 Affimed Therapeutics B-cell non-Hodgkin lymphoma Phase I (bispecific antibody) Heidelberg, Germany www. The program is funded by Incyte with Agenus eligible for potential milestones and 15% royalties, subject to reduction for certain third party obligations. Some preclinical studies had witnessed the effect of OX40 agonist in causing tumor regression and tumor rejection in animal models (26,48,50,66-73). “OX40 signaling leads to PD-L1 induction via IFN-γ-upregulation. About this Clinical Trial. Clinical Trial Categories Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination with Axitinib versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients with Metastatic Renal Cell Carcinoma. OX40 sufficient CD4 T cells express IFNαR and CD25 post TCR stimulation independent of extrinsic stimulus 28 Figure 5-3. The investigators will use antibodies generated in their lab against the canine OX40 checkpoint molecule to investigate its role in regulating cancer immunity in dogs, as a first step in advancing OX40 antibodies to clinical trials in dogs with cancer. Our results here impact the planning of future clinical trials of in situ vaccination with these two agents. Clinical Trial Categories Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination with Axitinib versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients with Metastatic Renal Cell Carcinoma. The potential for this therapy must have been transparently obvious to careful observers for at least the last 2 or 3 years. Treg cells function as immunosuppressive cells that limit the activity of effector T cells. LEXINGTON, Mass. The current phase 1 trials seem much more like phase 3 in scope. In the current study, KY1005 was seen to block T-cell-driven inflammation in the skin. Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. Anti-OX40 and CpG are both currently in phase-I trials as single agents. Innovent Receives an Approval from the US FDA to Initiate Clinical Trials for its Anti-OX40 Monoclonal Antibody IBI101. "We generated preclinical data demonstrating the efficacy of the antibody," Toniatti says. Disruption of the OX40 pathway led… Read more. OX40 itself does not have any enzymatic activity; upon activation, it associates with a number of adaptor proteins, including the TNF receptor-associated factors 2, 3, and 5 that activate. Upon administration, anti-OX40 monoclonal antibody MEDI0562 selectively binds to and activates the OX40 receptor. The researchers started by exploring dual combination immunotherapy. Research in mice has included the combination of an agonistic OX40 antibody (clone OX86) injected directly into a tumor in combination with an unmethylated CpG oligonucleotide, in which a TLR9 ligand activates expression of OX40 so that it can be affected. In the study published in Clinical Cancer Research, researchers found that concurrent treatment of mice bearing tumors that are refractory to anti-PD1 with anti-OX40 and anti-PD1 immunotherapies suppressed the therapeutic effect of anti-OX40 antibody, produced a cytokine storm-like event that made the mice lethargic, resulted in enlargement of their spleens, and led to an increase in the levels of the immune checkpoint proteins CTLA-4 and TIM-3 on T cells. Anaphylaxis caused by the GITR agonist antibody DTA-1 is dependent on GITR, IL-4, basophils, and platelet-activating factor. com AFM11 Affimed Therapeutics B-cell non-Hodgkin lymphoma Phase I (bispecific antibody) Heidelberg, Germany www. Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. 4-1BB is a 39 kDa transmembrane protein expressed by T lymphocytes, NK cells, dendritic cells, granulocytes, and mast cells. INBRX-109, a multivalent antibody targeting DR5 in Phase 1 for multiple oncology indications. Use our Cancer Immunotherapy Clinical Trial Finder to work with a Clinical Trial Navigator and match with clinical trials that might be right for you. OX40 is a member of the tumor necrosis factor (TNF) receptor superfamily that, when activated, may contribute to both adaptive and innate immune responses. Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from FDA for an anti-OX40 monoclonal antibody. The concurrent treatment of mice-bearing tumors that are refractory to. " GSK leads the multi-center clinical trial and all further clinical development. Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from FDA for an anti-OX40 monoclonal antibody. Concurrent treatment with OX40- and PD1-targeted cancer immunotherapies may be detrimental. Monoclonal antibodies specific for TrkA represent a first-in-class opportunity for the treatment of chronic pain, which has a high level of unmet need. CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the priority benefit of U. The study consisted of 3 arms with. ( C ) Splenocytes and prostate-draining lymph nodes (pooled for each group) were analyzed on day 35, and donor cell phenotype was determined by flow cytometry. Plasmid Protein Antibody Binding OX40 with - 8 currently in clinical trials. It is composed of two mRNAs that encode the heavy and light chains of this anti-Chikungunya antibody within Moderna’s proprietary lipid nanoparticle (LNP) technology. m "Worldwide clinical research on anti-OX40 antibodies is limited. We found that delivery of this. Currently there is no anti-RANKL inhibitors approved for marketing in China. In February 2018, an open-label extension study started to assess 8E12's longer-term safety and tolerability in participants in this trial who are ineligible for its. “Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. A monoclonal antibody against the chikungunya virus developed by researchers at Vanderbilt University Medical Center is the first monoclonal antibody encoded by messenger RNA to enter a clinical. a fragment of a monoclonal antibody specific for the desired target. Qualified Physician Investigators add to the understanding of what drives cancer and create innovative research applications that attack these drivers. The Current Understanding of the Endocrine Effects From Immune Checkpoint. clinical trial. The OX40 receptor is transiently expressed on activated T cells and serves as a late co-stimulatory receptor 1. 4, 2019 /PRNewswire/ -- Ichnos ('īk-nōz) Sciences today announced that it has completed enrollment of two Phase 2b clinical trials for two candidates in clinical development: ISB 830, an OX40 antagonist monoclonal antibody currently in development for the treatment of atopic dermatitis, and ISC 27864, a non-opioid, potent, selective and orally bioavailable inhibitor of. OX40 is a member of the tumor necrosis factor (TNF) receptor superfamily that, when activated, may contribute to both adaptive and innate immune responses. Clinical Trials Using Anti-OX40 Monoclonal Antibody. The antibody was well tolerated with minimal toxicity and observation of some tumor size reduction, although none of the patients showed an objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Request PDF on ResearchGate | Rationale for anti-OX40 cancer immunotherapy | Immune checkpoint blockade with antagonistic monoclonal antibodies (mAbs) targeting B7 immunoglobulin superfamily. The majority of irAEs were relatively minor (Grade 1 and 2), while all of moderate to severe (Grade 3 and 4) irAEs were due to treatment-induced lymphopenia that. We [4,5] and others have ex-tensively studied the functions of OX40 and OX40L in. IBI307 is an anti-RANKL antibody under development for the treatment of osteoporosis and lytic bone lesions associated with cancer metastasis. Mechanism 1: OX40 Forward Signaling in T Cells. Much attention in the field has been given to inhibitory check-. 0 mg kg) in healthy volunteers (HVs). CD40, GITR, OX40, CD137. Clinical Trial Categories Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination with Axitinib versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients with Metastatic Renal Cell Carcinoma. Sturgill, PhD, and William L. The potential for this therapy must have been transparently obvious to careful observers for at least the last 2 or 3 years. Official title: Phase I/Ib Study of Surgical Resection or Radiofrequency Ablation (RFA) of Metastatic Lesions in the Liver in Combination With Monoclonal Antibody to OX40 (MEDI6469) in Patients With Metastatic Colorectal Cancer. Currently, two 4-1BB agonist antibodies are in phase I and II clinical trials for NHL and melanoma, respectively (NCT01307267, NCT00612664), and one agonistic OX40 antibody is being studied in a phase I/II and phase II trial for prostate cancer and melanoma (NCT01303705, NCT01416844). Concurrent treatment with OX40 and PD1-targeted cancer immunotherapies may be detrimental 28 Aug 2017 Concurrent administration of the T-cell stimulating anti-OX40 antibody and the immune checkpoint inhibitor anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment outcomes in mice. The OX40 receptor is transiently expressed on activated T cells and serves as a late co-stimulatory receptor 1. This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. Your Message Will Go To Rachel Greenstein 650-723-2312. Mimicking the natural OX4 ligand (OX40L), anti-OX40 monoclonal antibody selectively binds to and activates the OX40 receptor. 46 OX40 enhances Bcl‐xL, but also upregulates Bcl‐2, Bfl‐1, survivin and aurora B kinase. 2 This may allow for the treatment of cancers such as. 85 In a phase I clinical trial, urelumab, a 4-1BB antibody, was evaluated in 83 patients with melanoma, renal cell carcinoma, ovarian and prostate cancer. Sturgill, PhD, and William L. OX40 and OX40L expression, interaction and molecular consequences. Within the OX40 agonist clinical trial, the traditional phase I trial design was abandoned, and 10 patients were treated per cohort, which ultimately allowed for statistically significant results. NK cell proliferation was also observed, with a 2-4. In the first anti-OX40 clinical trial, we have observed that the administration of anti-OX40 antibody increased the activation status of the CD8+ T cells as measured by the co-expression of CD38 and HLA-DR on the cycling cells. Overall, 81% of the patients were still alive at the six-month mark, and 71% at the nine-month mark. NCI's basic information about clinical trials explains the types and phases of trials and how they are carried out. NCT02318394). TNFR Agonists: A Review of Current Biologics Targeting OX40, 4-1BB, CD27, and GITR Elizabeth R. Concurrent treatment with OX40- and PD1-targeted cancer immunotherapies may be detrimental 28 August 2017 Concurrent administration of the T-cell stimulating anti-OX40 antibody and the immune. Major surgery less than 6 weeks prior to the first dose of study drug. There are currently five different molecules targeting OX40 in use in clinical trials against metastatic cancers, one of them being an OX40L-Fc and the others agonistic anti-OX40 antibodies. These include TIM3 inhibitors, LAG3 inhibitors, OX40 agonists, CD137 agonists, GITR agonists, and IDO inhibitors. Agonox proposes to construct a humanized version of this antibody by using the antibody humanization company, BioAtla LLC, as a subcontractor. The combination of anti-OX40 and CpG is currently studied in a phase I trial. The majority of irAEs were relatively minor (Grade 1 and 2), while all of moderate to severe (Grade 3 and 4) irAEs were due to treatment-induced lymphopenia that. The mechanism of IBI101 is different from that of anti-PD-1 antibodies. Recently, several groups have reduced clinical signs of autoimmunity in animal models by blocking the OX40-OX40-ligand interaction or depleting OX40 + T cells. The agonist activity can occur when the antibody binds the receptor in a manner that mimics the binding of the physiological ligand resulting in antibody-mediated agonism. Brief description of study. Promising results were observed, showing a strong bioactivity of the compound, although no antitumor responses. to expansion, deactivation, or cell death depending on the local milieu. Besides, clinical trials with OX40 agonists are ongoing in. "OX40 signaling leads to PD-L1 induction via IFN-γ-upregulation. Our group produced an OX40 mouse monoclonal antibody which showed intriguing properties in a Phase I clinical trial in Stage IV cancer patients. Anti-OX40 is a monoclonal antibody agonist of the OX40 receptor which is a member of the tumor necrosis factor (TNF) receptor superfamily expressed on the surface of activated T-cells. Since both OX40 and CTLA-4 are expressed on T cells in the tumor area, ADC-1015 is expected to induce strong tumor-directed immune activation. Announces Initiation of Phase 1 Clinical Trial of SL-279252 (PD1/OX40L). OX40 sufficient CD4 T cells express IFNαR and CD25 post TCR stimulation independent of extrinsic stimulus 28 Figure 5-3. Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI0562) Administered prior to Definitive Surgical Resection in Patients with Head and Neck Squamous Cell Carcinoma or Melanoma (AZ ESR-16-12559) Description: This clinical trial is the first to evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative. of antibodies which affect T cell regulation by targeting a diversity of coinhibitory and costimulatory molecules. OX40 sufficient CD4 T cells express CD25 at basal level 27 Figure 5-2. Innovent Receives IND Approval to Initiate Clinical Trials in China with its anti-OX40 Agonistic Antibody IBI101 and its anti-RANKL Antibody IBI307 PR. Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from FDA for an anti-OX40 monoclonal antibody. "Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. The all-comer study enrolled 51 patients who had incurable or metastatic solid tumors of any type. : The results of the clinical trials only support trials regarding the tolerability of combinatorial therapy, even when the objectives of determining the safety. A clinical trial has now been launched to test this vaccination approach in combination with low dose local radiation in people with lymphoma. NCT02318394). TNFRSF4 is receptor for TNFSF4 / OX40L / GP34 and can interacts with TRAF2, TRAF3 and TRAF5. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma. 35 (Aug 2017 conference news, Dec 2016 company release). Innovent Receives an Approval from the US FDA to Initiate Clinical Trials for its Anti-OX40 Monoclonal Antibody IBI101. To improve response rates and to overcome resistance, novel second- and third-generation immuno-oncology drugs are currently evaluated in ongoing phase I/II trials (either alone or in combination) including novel inhibitory compounds (e. Brief description of study. A phase 1 clinical trial testing an antibody agonist of OX40 with cyclophosphamide and single fraction RT (8 Gy) in metastatic prostate cancer patients is currently ongoing, though no longer recruiting (NCT01642290). Early research results spurred Providence to launch the world's first clinical trial of anti-OX40 in humans. The studies, published in Clinical Cancer Research and Cancer Immunology Research, investigated whether combining an antibody targeting the tumor necrosis factor receptor superfamily member 4 (also called OX40) with an anti-PD1 antibody can improve antitumor responses and survival outcomes. m "Worldwide clinical research on anti-OX40 antibodies is limited. 107,126 A phase I/II trial combining INCAGN01876 with. The majority of irAEs were relatively minor (Grade 1 and 2), while all of moderate to severe (Grade 3 and 4) irAEs were due to treatment-induced lymphopenia that. Recombinant HEK 293T cells stably expressing an exogenous human OX40 (CD134) gene for drug screening and biological assays. Phase I Clinical Trial sponsorship has evolved together with the current ICH-GCP guidelines, under which the ReiThera’s CTU. Also, a number of combinations of immunotherapies are being looked at, including all of the above agents with anti-PD-1 or anti-PD-L1 antibodies, as well as combinations of targeted therapies with anti-PD-1 or anti-PD-L1 antibodies. It has received US FDA's IND approvals for IBI308 (Sintilimab, an anti-PD-1 antibody) in January 2018 and IBI188 (an anti-CD47 antibody) in September 2018 respectively. OX-40 is a 50 kDa type I membrane glycoprotein and a member of the TNF receptor superfamily. Ghobrial, 1,5 Xiang Xiao, 1 and Xian Chang Li 1,5. Product DescriptionsEdit. How PF-04518600 works. As New Jersey's only National Cancer Institute-designated Comprehensive Care Center, Rutgers Cancer Institute along with its partner RWJ Barnabas Health offer access to cutting-edge clinical trials throughout the state of New Jersey. Pre-clinical studies have shown that OX40 agonist synergizes with radiation and cyclophosphamide to increase survival. (Information about the trial is available online. Patients had either progressed on standard therapy or a clinical trial of a novel agent was a standard treatment for their tumor type and setting. TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury Peixiang Lan, 1 Yihui Fan, 1 Yue Zhao, 1 Xiaohua Lou, 1 Howard P. We [4,5] and others have ex-tensively studied the functions of OX40 and OX40L in. Announces Initiation of Phase 1 Clinical Trial of SL-279252 (PD1/OX40L). Croft is a Fellow of the American Asthma Foundation (formerly the Sandler Asthma Foundation). This is first of an anticipated stream of clinical trials, focused on autoimmune diseases, immune-oncology, haematology and infectious disease. Signaling pathways downstream of OX40 14 Figure 4. The clinical trials on this list are studying Anti-OX40 Antibody BMS 986178. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. Provided herein is a method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and an OX40 binding agonist. 98,99 A study in 2014 further identified that OX86 depletes tumor-resident Tregs but not CD8 + T cells, likely because of the preferential expression of OX40 on Tregs compared with effector T cells in the tumor 100 ; a version of this antibody. INBRX-106 has demonstrated strong single agent activity in preclinical models that do not respond to blockade of the PD-1/PD-L1 axis, and this activity is improved by addition of a PD-1 blocking antibody. Our results here impact the planning of future clinical trials of in situ vaccination with these two agents. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. Listing a study does not mean it has been evaluated by the U. A Phase II clinical trial evaluating either pinatuzumab vedotin or polatuzumab vedotin in combination with Rituxan® (Rituximab) for relapsed or refractory follicular non-Hodgkin's lymphoma and relapsed or refractory diffuse large B-cell lymphoma is ongoing. Of the trials investigating Agonistic Anti-OX40 Monoclonal Antibody INCAGN01949, 2 are phase 1/phase 2 (1 open). This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. Clinical Trials Using Anti-OX40 Monoclonal Antibody. CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). Disruption of the OX40 pathway led… Read more. Because anti-OX40 therapy augments the development, activity, and survival of effector lymphocyte populations, it is possible that the combination of anti-OX40 with checkpoint blockade will produce a higher frequency of irAEs than the respective individual treatments. Kymab Announces Promising Results from Initial Clinical Study of New Antibody KY1005 for Treatment of Autoimmune Diseases Top-line Phase I data demonstrated. Sturgill, PhD, and William L. The treatment was very well tolerated. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. 4, 2019 /PRNewswire/ -- Ichnos ('īk-nōz) Sciences today announced that it has completed enrollment of two Phase 2b clinical trials for two candidates in clinical development: ISB 830, an OX40 antagonist monoclonal antibody currently in development for the treatment of atopic dermatitis, and ISC 27864, a non-opioid, potent, selective and orally bioavailable inhibitor of. School of Medicine in the US are this month starting a clinical trial using human patients. implicated in disease activity. Posted Feb 17, 2017. As compared to an antibody the murine OX40L:Ig fusion protein has a short half-life (approximately 24hrs), therefore we first compared injecting this protein every day for 5 consecutive days versus 5 injections delivered every other day (these injections were initiated 3 days after tumor inoculation). Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. Since both OX40 and CTLA-4 are expressed on T cells in the tumor area, ADC-1015 is expected to induce strong tumor-directed immune activation. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Glenmark Pharmaceuticals Announces Initiation of a Phase 2b Trial of GBR 830, a First-in-Class, Investigational, Anti-OX40 Monoclonal Antibody for the Treatment of Moderate-to-Severe Atopic Dermatitis. Our results here impact the planning of future clinical trials of in situ vaccination with these two agents. 4-1BB is a 39 kDa transmembrane protein expressed by T lymphocytes, NK cells, dendritic cells, granulocytes, and mast cells. NCT03217747: Avelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients With Advanced Malignancies NCT03217747 Breast Cancer Type: HER2+ , HR+ & HER2-negative, Triple Negative. Our group produced an OX40 mouse monoclonal antibody which showed intriguing properties in a Phase I clinical trial in Stage IV cancer patients. Kymab's therapeutic antibody KY1005 has successfully completed dosing of the 24th subject in its first clinical study. Data from the first anti-OX40 trial, although indicating a strong bioactivity of the compound, fail to suggest a dramatic anti-tumour efficacy, as opposed to what was reported for anti-PD1/PDL1 mAbs. The clinical trials on this list are studying Anti-OX40 Antibody BMS 986178. This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. (NYSE:PFE) today announced results from a Phase 1b trial of Pfizer’s investigational immunotherapy agent utomilumab (the proposed non-proprietary name for PF-05082566), a 4-1BB (also called CD137) agonist, in combination with pembrolizumab, a PD-1 inhibitor, in patients with advanced solid tumors. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. GITR, OX40, CTLA-4, PD-1, TIM-3 and LAG-3 – Proprietary mammalian B cell platform generates fully human antibodies with desirable drug-like behavior. 5 fold proliferation increase. CTX-471 profoundly reprograms the tumor microenvironment, increasing CD8+ T cell infiltration and penetration while reducing T-cell exhaustion. Receptor activation induces proliferation of memory and effector T lymphocytes. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. But subsequent clinical data have been anything but overwhelming, and. In the first anti-OX40 clinical trial, we have observed that the administration of anti-OX40 antibody increased the activation status of the CD8+ T cells as measured by the co-expression of CD38 and HLA-DR on the cycling cells. A monoclonal antibody against the chikungunya virus developed by researchers at Vanderbilt University Medical Center is the first monoclonal antibody encoded by messenger RNA to enter a clinical. Authors of patent US2018256711A1 propose a method to eradicate cancer that utilizes anti-OX40 agonist antibody in combination with anti-PD-L1 antagonist antibody. Provided herein is a method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a PD-1 axis binding antagonist and an OX40 binding agonist. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality innovative medicines for the treatment of oncology, autoimmune and other major diseases, today announced that the first patient has been dosed in a Phase I clinical trial of IBI101, a recombinant. TNFRSF4 is receptor for TNFSF4 / OX40L / GP34 and can interacts with TRAF2, TRAF3 and TRAF5. Anti-OX40 antibodies have recently shown promise in a phase I clinical trial at our institution , and are currently being evaluated in a Phase I trial in combination with radiation that uses the optimal timing described in this manuscript. The trial will use one in hundredth of the dose that was used for systemic administration of anti-OX40 since they will be injecting directly into the tumour. A phase I clinical trial in human patients showed no clinical responses by RECIST criteria, although 18 of 30 patients showed stable disease or regression in at least 1 lesion. Recombinant HEK 293T cells stably expressing an exogenous human OX40 gene for drug screening and biological assays. His research on OX40/OX40L interactions controlling the generation and activity of Th2 cells is cited by the Foundation as one of their major breakthroughs, and led to clinical trials of antagonists of OX40L in asthma. "Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. Our group produced an OX40 mouse monoclonal antibody which showed intriguing properties in a Phase I clinical trial in Stage IV cancer patients. Lead author, Sandrine Aspelaugh, explains why blocking the OX40 molecule could become an important new approach in immunotherapy in the EJC’s January podcast. Any reference in these archives to AstraZeneca products or their uses may not reflect current medical knowledge and should not be used as a source of information on the present product label, efficacy data or safety data. To date, much of the agonistic antibody in clinical and pre-clinical studies target TNF family members, such as OX40, CD27, 4-1BB and DR5. TNFRSF4 is receptor for TNFSF4 / OX40L / GP34 and can interacts with TRAF2, TRAF3 and TRAF5. In a melanoma murine model, concurrent administration of anti-41BB and anti-CTLA-4 antibodies resulted in prolonged survival. to expansion, deactivation, or cell death depending on the local milieu. Recently, immuno-oncology drugs have demonstrated significant improvements over standard-of-care therapies in certain malignancies, exemplified by FDA approvals for anti-CTLA-4, anti-PD-1, and anti-PD-L1 mAbs (). Phase Ib Study of a Monoclonal Antibody to OX40 (MEDI0562) Administered prior to Definitive Surgical Resection in Patients with Head and Neck Squamous Cell Carcinoma or Melanoma (AZ ESR-16-12559) Description: This clinical trial is the first to evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative. Phase I Clinical Trial sponsorship has evolved together with the current ICH-GCP guidelines, under which the ReiThera’s CTU. Combination Immunotherapy with Vaccination and Anti-OX40 Antibody Improves Survival in Syngeneic Glioma-Bearing Mice. About this Clinical Trial. New ADAPTIR Candidate APVO603 is a Dual-Agonistic Bispecific Antibody Targeting 4-1BB and OX40 APVO603 is Designed to Induce Synergistic Effects on Immune Responses with Potential to Enhance Anti-Tumor Immune Response Against Solid Tumors SEATTLE , Sept. Example 4 - Phase la clinical trial to establish safety and tolerability of antagonistic anti- OX40 antibody A phase la clinical study was undertaken to evaluate the safety and tolerability of single ascending doses of an antagonistic anti-OX40 antibody (0. Federal Government. It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. Flaherty , Mark Wencel , Jack Wanger , Thomas Neff , Frank Valone , John. Sturgill, PhD, and William L. We look forward to learning. The third antibody is GBR 830, a best in class OX40 antagonist for autoimmune diseases which recently entered. The studies were published in Clinical Cancer Research and Cancer Immunology Research, two. Clinical Trials Ongoing Including Combination Therapy. The founders of AgonOx were the first to identify and develop anti-OX40 as a cancer therapy and, along with the Providence Cancer Institute, brought the first OX40 agent into clinical trials. Anaphylaxis caused by the GITR agonist antibody DTA-1 is dependent on GITR, IL-4, basophils, and platelet-activating factor. Here's some strong evidence for what could be the next wave of immuno-oncology: combining a TLR9 ligand with an OX40 antibody. Concurrent administration of the T-cell stimulating anti-OX40 antibody and the immune checkpoint inhibitor anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment. TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury Peixiang Lan, 1 Yihui Fan, 1 Yue Zhao, 1 Xiaohua Lou, 1 Howard P. TNFR Agonists: A Review of Current Biologics Targeting OX40, 4-1BB, CD27, and GITR Elizabeth R. "And we were the first to show convincingly that OX40 and PD1 is a good combination. A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley) Purpose. Patients had either progressed on standard therapy or a clinical trial of a novel agent was a standard treatment for their tumor type and setting. Proposed Mechanism of Disease. discovering antibodies that inhibit OX40 and do not have agonistic properties which would lead to unwanted side effects has been challenging for the industry. Concurrent administration of the T-cell stimulating anti-OX40 antibody and the immune checkpoint inhibitor anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment. "Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. Research in mice has included the combination of an agonistic OX40 antibody (clone OX86) injected directly into a tumor in combination with an unmethylated CpG oligonucleotide, in which a TLR9 ligand activates expression of OX40 so that it can be affected. However, the tumor secretes a number of suppressive signals as a protective mechanism against its destruction, one of which is IDO. However, the contributions of OX40 and OX40L to the development of T1D remain to be studied. Shu-juan Zhou 1, Jia Wei 1, Shu Su 1, Fang-jun Chen 1, Yu-dong Qiu 2 , Bao-rui Liu 1. OX40 sufficient CD4 T cells express CD25 at basal level 27 Figure 5-2. The program is funded by Incyte with Agenus eligible for potential milestones and 15% royalties, subject to reduction for certain third party obligations. NK cell proliferation was also observed, with a 2-4. This antibody was further tested in phase I clinical trials in 30 patients where the mouse anti-human OX40 antibody was given on days 1, 3, and 5 at 0. OX40 itself does not have any enzymatic activity; upon activation, it associates with a number of adaptor proteins, including the TNF receptor–associated factors 2, 3, and 5 that activate. To date, much of the agonistic antibody in clinical and pre-clinical studies target TNF family members, such as OX40, CD27, 4-1BB and DR5. 9B12, a murine IgG anti-OX40 antibody, was studied in a phase I clinical trial (NCT01644968) for patients with solid tumor refractory to conventional therapy. 2 This may allow for the treatment of cancers such as. , a wholly. Also, a number of combinations of immunotherapies are being looked at, including all of the above agents with anti-PD-1 or anti-PD-L1 antibodies, as well as combinations of targeted therapies with anti-PD-1 or anti-PD-L1 antibodies. The physicians at Weill Cornell Medicine/NewYork-Presbyterian are dedicated to the pursuit of breakthrough research, and the safe and ethical management of clinical trials. Trial 4K-16-5 Phase II Randomized Double Blind Trial of PF 04518600, an OX40 Antibody, in Combination with Axitinib versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients with Metastatic Renal Cell Carcinoma. Clinical Trial Categories Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination with Axitinib versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients with Metastatic Renal Cell Carcinoma. "OX40 signaling leads to PD-L1 induction via IFN-γ-upregulation. The concurrent treatment of mice-bearing tumors that are refractory to. Antibodies engaging GITR or OX40 result in significant tumor protection in preclinical models. 1 to 2 mg/kg in the first-in-human clinical trial. "Worldwide clinical research on anti-OX40 antibodies is limited so far. A phase I clinical trial testing the B-raf inhibitor vemurafenib combined with the anti-CTLA-4 antibody ipilimumab was terminated early due to hepatotoxicity ; however, preliminary data from a combination trial of ipilimumab with the BRAF inhibitor dabrafenib indicate that this combination can be tolerable. Shattuck Labs, Inc. The Hu GEMM PD-1/OX40 mouse provides a translational humanized drug target mouse model for testing human-specific combination therapies. Qualified Physician Investigators add to the understanding of what drives cancer and create innovative research applications that attack these drivers. Various other combination therapies have since been tested preclinically, and that work is continuing. Besides, clinical trials with OX40 agonists are ongoing in. Dual Immunotherapy. Agonox proposes to construct a humanized version of this antibody by using the antibody humanization company, BioAtla LLC, as a subcontractor. responses, humanised OX40 agonist monoclonal antibodies are currently being introduced in early phase clinical trials for various cancer types (e. It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. "Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. CD137, or 4-1BB, is a tumor necrotic factor receptor found primarily on activated T cells, natural killer (NK) cells, and myeloid cells. 5 fold proliferation increase. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Mol Ther 2014; 22:1056. , a wholly. The selected product used in this study reactivates the cancer-specific T cells by injecting microgram amounts of CpG oligonucleotide, a ligand for TLR9, and an anti-OX40 antibody directly into the tumor. Notably, an anti-OX40 monoclonal antibody (KHK4083) has been administered to patients with PS in a phase I clinical trial with improved effects. The OX40 agonist has shown antitumor efficacy in preclinical trials and is believed to have the ability to combine effectively with therapeutic cancer vaccines, as well as immuno-oncology targets. Lund, Sweden, July 19, 2018 – Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, today announced that the company has submitted a clinical trial authorization (CTA) application to the relevant regulatory authorities to start a phase I study of its wholly-owned bispecific drug candidate ATOR-1015. Monsour, 2 Xiaolong Zhang, 1 Yongwon Choi, 3 Yaling Dou, 1 Naoto Ishii, 4 Rafik M. 1 synonym for monoclonal: monoclonal antibody. INCAGN01949 Demonstrates Affinity for OX40 and Recognizes Primary Activated T Cells. Ghobrial, 1,5 Xiang Xiao, 1 and Xian Chang Li 1,5. "Innovent was built according to international R&D and production standards and has been exploring the latest cutting-edge research in the area of biopharmaceutical development. A phase I clinical trial has shown that anti-OX40 mAb was well tolerated and induced proliferation of CD8 and CD4 non-Treg cells in the peripheral blood (PB). This antibody binds its target, and causes activation of a subset of T-cells known as T effector cells and reduces the activity of a different subset of T-cells known as T regulatory cells (T regs). OX40 Agonism. Immunotherapy for cancer using antibodies to enhance T. It binds with OX40, a receptor on the surface of specialized immune T-cells that fight invaders. The OX40 project continues with the hope that in the next decade a new therapy will be available for patients with cancer. Methods: This is a Phase 1 study evaluating MEDI0562, a humanized OX40 agonist mAb, in adult pts with advanced solid tumors. a phase I clinical trial is evaluating Venclexta in combination with Gazyva for. NCT02318394). NK cell proliferation was also observed, with a 2-4. Type I IFN signaling 18 Figure 5-1. Zamarin D, Holmgaard RB, Subudhi SK, et al. The all-comer study enrolled 51 patients who had incurable or metastatic solid tumors of any type. Mimicking the natural OX4 ligand (OX40L), anti-OX40 monoclonal antibody selectively binds to and activates the OX40 receptor. This combination of a TLR9 ligand and anti-OX40 antibody effectively treated spontaneous breast cancers and distant sites of established tumors. Anti-OX40 and CpG are both currently in phase-I trials as single agents. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12/30 patients. Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. The OX40 molecule is a co-stimulatory receptor expressed on T-cells that can lead to proliferation and enhancement of T-cell effector function when triggered with an agonistic antibody. OX40 is a member of the tumor necrosis factor (TNF) receptor superfamily that, when activated, may contribute to both adaptive and innate immune responses. This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. It was a real collaboration, ORBIT and GSK labs working together. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival. Shattuck Labs, Inc. Federal Government. A phase I clinical trial has shown that anti-OX40 mAb was well tolerated and induced proliferation of CD8 and CD4 non-Treg cells in the peripheral blood (PB). In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Prior treatment with an anti-CD137, or OX40 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways except anti-PD1, anti-PDL1/2 and CTLA-4 antibodies. The program is funded by Incyte with Agenus eligible for potential milestones and 15% royalties, subject to reduction for certain third party obligations. A monoclonal antibody against the chikungunya virus developed by researchers at Vanderbilt University Medical Center is the first monoclonal antibody encoded by messenger RNA to enter a clinical. OX40 antibodies in murine models with an intact immune system have demonstrated tumor regression. Major surgery less than 6 weeks prior to the first dose of study drug. Shattuck Labs, Inc. Regulatory T-cells suppress the. TRAF2, TRAF3 and TRAF5 associate with OX40 via a cytoplasmic QEE motif, 45 TRAF3 mediating NF‐κB activation. Innovent Biologics, Inc. GBR 830 is an investigational monoclonal antibody designed to inhibit OX40, a costimulatory immune checkpoint receptor expressed on activated T cells and memory T cells. Qualified Physician Investigators add to the understanding of what drives cancer and create innovative research applications that attack these drivers. The investigators will use antibodies generated in their lab against the canine OX40 checkpoint molecule to investigate its role in regulating cancer immunity in dogs, as a first step in advancing OX40 antibodies to clinical trials in dogs with cancer. 9B12 is a murine IgG monoclonal agonistic antibody against OX40 that was studied in a phase I clinical trial in 30 patients with metastatic solid. COMBINATION THERAPY COMPRISING OX40 BINDING AGONISTS AND PD-1 AXIS. In preclinical studies, OX40 agonists have been shown to stimulate immune effector and memory T cell function while attenuating immunosuppressive function of regulatory T cells, leading to anti-tumor activity. Just a couple of years ago Ox40 was billed as one of the most promising targets in a new wave of immuno-oncology projects. OX40 antibody treatment was well tolerated with. Clinical development of OX40 agonists started in 2006 with a murine antihuman OX40 (anti-hOX40) mAb. Innovent will be among one of a few companies pursuing the development of OX40 agonists in early stage clinical trials globally. mRNA-1944 encodes a fully human IgG antibody originally isolated from B cells of a patient with a prior history of potent immunity against Chikungunya infection. 3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137.