Ox40 Antibody Clinical Trial

Pre-clinical data confirms that IBI101 has a clear mechanism of action that enhances the activation of effector T cells and mediates the clearance of regulatory T cells, thus inhibiting the growth of tumor cells. Anaphylaxis caused by the GITR agonist antibody DTA-1 is dependent on GITR, IL-4, basophils, and platelet-activating factor. cDNA clones were isolated from an expression library using the MRC OX40 mAb and the protein sequence for the OX40 antigen deduced. Of the nineteen patients who were treated with 450 million anti-BCMA CAR T cells, all but one responded, and half of these patients (9) had complete responses. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. 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. 3 A combination phase I trial of MOXR0916 (OX40 agonist) and atezolizumab revealed two objective responses. These collections are currently recommended for research applications like FACS, functional assays, ELISA, Immunohistochemistry and Western Blot, and some are in the process of being validated for in vivo use. 107,126 A phase I/II trial combining INCAGN01876 with. One of the goals of the planned clinical trial is to assess the safety of the combination. FS120 is a potential best-in-class dual agonist bispecific antibody, targeting OX40 and CD137 (4-1BB). News provided by. 4 Phase I/II clinical trials with eight OX40 agonists under development by Pfizer. Abstract Background. Hexameric recombinant OX40L is fully capable of activating OX40-signaling like OX40 agonistic antibodies, with no dose-limiting toxicity of such an OX40 antibody in an early clinical trial. 1 to 2 mg/kg in the first-in-human clinical trial. The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China; 2. Agenus and Incyte will share all costs and profits for the GITR and OX40 antibody programs on a 50:50 basis, with Agenus eligible for potential milestones; TIM-3 and LAG-3 are royalty-bearing programs to be funded by Incyte, with Agenus eligible for potential milestones and royalties. NSCLC Cohorts (CIT-Naïve): Participants with histologically confirmed incurable, advanced NSCLC not previously treated with anti-PD−L1/PD-1 and/or with anti-CTLA−4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD−L1/PD-1 antibody is considered an acceptable treatment option (if CIT [including anti-PD−L1/PD-1 agents] is approved as treatment for NSCLC by local regulatory authorities). In a week that saw major pipeline culls. Clinical Trials Ongoing Including Combination Therapy. OX40 sufficient CD4 T cells express IFNαR and CD25 post TCR stimulation independent of extrinsic stimulus 28 Figure 5-3. Shattuck Labs, Inc. Shrimali et al. Antibodies engaging GITR or OX40 result in significant tumor protection in preclinical models. MOXR0916 is an agonist, effector-competent humanized IgG1 antibody against OX40. Type I IFN signaling 18 Figure 5-1. 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. NCT02318394). Given its role in anti-cancer immune responses, humanised OX40 agonist monoclonal antibodies are currently being introduced in early phase clinical trials for various cancer types (e. Phase I trials of agonistic CD40 mAb alone and in com-bination with standard therapies have shown promise in a variety of solid tumors, encouraging further studies of this approach in combination with other immune-targeting therapies [30–32]. clinical trial. The Bispecific Antibody Pipeline Congress unites key opinion leaders including regulators, clinicians, and industry experts to deepen our understanding of bispecific therapeutics and exchange innovative ideas to foster meaningful research collaborations. OX40 is a TNF-receptor family member that is expressed on activated CD4+ and CD8+ T cells. As OX40, at a high dose of 150 μg, itself displayed antitumor activity (Supplemental Figure 3), we sought to isolate the effect of PancVAX from that of OX40 and, importantly, define the minimal effective dose of the OX40 antibody that could synergize with PancVAX and anti–PD-1. 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. OX40 functions on effector T cells to enhance their activity and proliferation. : The results of the clinical trials only support trials regarding the tolerability of combinatorial therapy, even when the objectives of determining the safety. This improvement was also clearly demonstrated by a reduction in paw swelling in anti-OX40 Fab′PEG-treated mice ( Fig. The OX40 project continues with the hope that in the next decade a new therapy will be available for patients with cancer. Search Results Title: J13101 "A Phase 1/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination with Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors". 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. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. Sample size antibodies available through Novus Biologicals. There was no biomarker-based. Pre-clinical studies further demonstrate improved pharmacologic and anti-tumor activity compared to antibody-based PD-1 blockade, either alone or in combination with antibody-based OX40 stimulation. PF-04518600 is a fully human Immunoglobulin G2 (IgG2) agonistic monoclonal antibody that is highly selective for human OX40 (CD134). Merus' innovative bispecific antibody therapeutics referred to as Biclonics ® are designed to recruit the immune system to kill cancer cells and tip the balance in favor of patients thanks to more effective treatments that have fewer side effects. CpG and anti-OX40 are both already being studied in clinical trials. CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). Experimental Design: We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade. Further investigation revealed that adding an agonistic anti-OX40 antibody would provide a synergistic effect and simulate an even a greater antitumor immune response. Glenmark Pharmaceuticals, a global pharmaceutical company, presented findings from a phase 2a study of GBR 830, an investigational anti-OX40 monoclonal antibody, at the 2018 American Academy of Dermatology (AAD) Annual Meeting in San Diego. OX40 (CD134) is a co-stimulatory molecule and several anti-OX40 agonistic monoclonal antibodies are being tested in early phase clinical trials. 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. 45 Since OX40 lacks the YMXM PI3K binding site of CD28 and ICOS, it is not clear whether OX40 activates PI3K directly or indirectly. OX40/OX40L is a pair of important positive costimulatory signal molecules in the second signal system of T cells. PD-1 Axis Binding Antagonists. Given existing data that GVAX generates effective systemic antitumor immunity, we hypothesized that adding anti-OX40 antibody would strengthen and prolong the activation of tumor-specific lymphocytes. 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. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Shattuck Labs, Inc. TNFR Agonists: A Review of Current Biologics Targeting OX40, 4-1BB, CD27, and GITR Elizabeth R. Innovent Announces First Patient Dosed in a Phase I Clinical Trial of an Anti-OX40 Antibody By Published: Feb 13, 2019 6 :00 p. 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. 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. Agenus and Incyte will share all costs and profits for the GITR and OX40 antibody programs on a 50:50 basis, with Agenus eligible for potential milestones; TIM-3 and LAG-3 are royalty-bearing programs to be funded by Incyte, with Agenus eligible for potential milestones and royalties. of an agonist antibody to OX40 in patients with advanced cancer. OX40 antibodies in murine models with an intact immune system have demonstrated tumor regression. (Information about the trial is available online. Leave a Reply Cancel reply. Given its role in anti-cancer immune responses, humanised OX40 agonist monoclonal antibodies are currently being introduced in early phase clinical trials for various cancer types (e. "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 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. Base on its antitumor effects in a variety of preclinical models, anti-OX40 co-stimulatory antibody is in clinical development, a phase I clinical trial of anti-OX40 antibody therapy showed it was. Table 2 is a summary of the published or presented trials investigating these various checkpoint antibodies in cancer immunotherapy. NSCLC Cohorts (CIT-Naïve): Participants with histologically confirmed incurable, advanced NSCLC not previously treated with anti-PD−L1/PD-1 and/or with anti-CTLA−4 (investigational or approved), for whom a clinical trial of an investigational agent in combination with an anti-PD−L1/PD-1 antibody is considered an acceptable treatment option (if CIT [including anti-PD−L1/PD-1 agents] is approved as treatment for NSCLC by local regulatory authorities). OX-40 is a 50 kDa type I membrane glycoprotein and a member of the TNF receptor superfamily. 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. OX40 - Tumour necrosis factor (TNF) receptor family. Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from FDA for an anti-OX40 monoclonal antibody. 3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. 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. OX40 Agonism. a phase I clinical trial is evaluating Venclexta in combination with Gazyva for. About GBR 830 in Atopic Dermatitis GBR 830 is designed to inhibit OX40, a costimulatory immune checkpoint receptor expressed on activated T cells and memory T cells. 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. Costimulatory signals are essential for T cell activity, and binding between OX40 and OX40L is a biomarker for the severity of autoimmune diseases. 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. 107,126 A phase I/II trial combining INCAGN01876 with. Recombinant HEK 293T cells stably expressing an exogenous human OX40 (CD134) gene for drug screening and biological assays. Treg cells function as immunosuppressive cells that limit the activity of effector T cells. (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune checkpoint antibodies and cancer vaccines, today announced that the first patient has been dosed in a Phase 1/2 clinical trial of the anti-OX40 agonist antibody INCAGN1949. Here's some strong evidence for what could be the next wave of immuno-oncology: combining a TLR9 ligand with an OX40 antibody. OX40 Agonism. 4-1BB is a 39 kDa transmembrane protein expressed by T lymphocytes, NK cells, dendritic cells, granulocytes, and mast cells. OX40 / TNFRSF4 contains four TNFR-Cys repeats. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. OX40 antibodies are being developed by several pharmas. About this Clinical Trial. 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. "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. Tumor necrosis factor receptor superfamily member 4 (TNFRSF4) is also known as ACT35 antigen, OX40L receptor, TAX transcriptionally-activated glycoprotein 1 receptor, CD antigen CD134, OX40. These antibodies modify regulatory checkpoints of the immune system, and are able to increase the body's immune response to cancer. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. TIL express TNFR molecules but the endogenous ligand is often limited. Anti-OX40 agonistic monoclonal antibodies and OX40L-Fc fusion proteins are currently tested in early phase cancer clinical trials. For this reason, agonist antibodies targeting CD137, CD357, CD134 and CD27 have received considerable attention for. Since Agonox did a deal with an AstraZeneca, the company has moved into new areas of research. 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. Based on our data GBR 830 is the best in class OX40 antagonistic antibody. Much attention in the field has been given to inhibitory check-. Today, MedImmune is investing in further development of OX40, and along with Providence and AgonOX, is expanding clinical trials for patients with melanoma, breast cancer, and prostate cancer. 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). The purpose of this study is to test the safety of the anti-OX40 antibody, MEDI6469, given prior to surgery in patients with advanced head and neck squamous cell carcinoma. TLR9 agonists and anti-OX40 antibodies are currently under clinical development for cancer treatment. 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. OX40 sufficient CD4 T cells express IFNαR and CD25 post TCR stimulation independent of extrinsic stimulus 28 Figure 5-3. 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. (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. Most notably, CTX-471 is able to induce the complete eradication of large, established tumors where other preclinical CD137 antibodies and antibodies against PD-1, PDL, CTLA, and OX40 have minimal effect. As of 2017, more than 500 clinical trials involving PD-1 and PD-L1 inhibitors have been conducted in more than 20,000 patients. IGM Biosciences Initiates First-in-Human Phase 1 Clinical Trial of IGM-2323 for the Treatment of Relapsed/Refractory B Cell Non-Hodgkin’s Lymphoma October, 2019 Read More. 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. OX-40 is a 50 kDa type I membrane glycoprotein and a member of the TNF receptor superfamily. This phase Ib/II trial studies the side effects and best dose of anti-OX40 antibody PF-04518600 (OX40) and how well it works alone or in combination with venetoclax, avelumab, glasdegib, gemtuzumab ozogamicin, and azacitidine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Sturgill, PhD, and William L. Materials and Methods Clinical trial ID#NCT01644968 Clinical trial was designed and performed as described in Supplementary Materials and Methods. We [4,5] and others have ex-tensively studied the functions of OX40 and OX40L in. TIL express TNFR molecules but the endogenous ligand is often limited. The combination of a TLR ligand and an anti-OX40 antibody cured multiple types of cancer, in mice null A new solid tumor cancer vaccine clinical trial is fundamentally different than previous research studies. OX40 Agonism. The OX40 project continues with the hope that in the next decade a new therapy will be available for patients with cancer. Regulatory T-cells suppress the. Cancer "vaccine" makes tumours vanish. , a wholly. OX40 antibody treatment was well tolerated with. Patient-centric focus brings the newest clinical trial options to patients at a rapid pace. Immunotherapy for cancer using antibodies to enhance T. Home News Incyte Takes on Global Responsibility for Agenus' GITR and OX40 Antibody Immuno-oncology firm Agenus started the Phase I/II clinical trial with INCAGN1949 in patients with solid. For this reason, agonist antibodies targeting CD137, CD357, CD134 and CD27 have received considerable attention for. One of the goals of the planned clinical trial is to assess the safety of the combination. OX40 sufficient CD4 T cells express CD25 at basal level 27 Figure 5-2. 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. Toll-like receptor 9 ligands have been shown to promote expression of OX40. antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Hexameric recombinant OX40L is fully capable of activating OX40-signaling like OX40 agonistic antibodies, with no dose-limiting toxicity of such an OX40 antibody in an early clinical trial. Cancer "vaccine" makes tumours vanish. discovering antibodies that inhibit OX40 and do not have agonistic properties which would lead to unwanted side effects has been challenging for the industry. the second agent - an antibody that binds to OX40. 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. 77 Etaracizumab, a monoclonal antibody against integrin αvβ3 has shown efficacy in a phase I trial in a variety of tumors, although a subsequent phase II trial showed no improvement in PFS or OS with etaracizumab. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma. 1 to 2 mg/kg in the first-in-human clinical trial. In addition, Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from US FDA for an anti-OX40 monoclonal antibody. Agonox proposes to construct a humanized version of this antibody by using the antibody humanization company, BioAtla LLC, as a subcontractor. IBI307 is an anti-RANKL antibody under development for the treatment of osteoporosis and lytic bone lesions associated with cancer metastasis. Antonyms for monoclonal. Hence, as these immune-enhancing antibodies are evaluated in human clinical trials there will likely be several used to augment tumor immunity (e. CpG and anti-OX40 are both already being studied in clinical trials. Our robust pipeline includes investigational therapies in varied stages of clinical development, from recently approved products to earlier-stage molecules in clinical trials. - The Antibody has Been Well Tolerated With a Favourable Pharmacokinetic Profile - GBR 830 is the First OX40 Antagonist to Complete Phase 1 Clinical Studies Glenmark Pharmaceuticals S. Required fields are marked *. 5 fold proliferation increase. KY1005 is an antagonist of OX40-Ligand (OX40L) with the potential to treat a number of immune mediated and inflammatory disorders (autoimmune diseases). NYU Langone's Division of Gastroenterology and Hepatology offers patients opportunities to take part in clinical trials, providing access to studies evaluating novel new treatments and approaches to many gastrointestinal and liver diseases and conditions. OX40 receptor activation induces proliferation of memory and effector T-lymphocytes. 1 Here we present updated safety data and clinical activity for pts treated during the dose-escalation phase. Explore → INBRX-105, a multispecific antibody engineered to focus 41BB agonism to sites of PD-L1 expression in Phase 1 for multiple oncology indications. Renal cell carcinoma is a type of kidney cancer that affects mainly elderly population. The immune stimulating properties of OX40 agonists could provide an immunologic stimulus to overcome some of the immunosuppressive properties of cancer, and thus. Hexameric recombinant OX40L is fully capable of activating OX40-signaling like OX40 agonistic antibodies, with no dose-limiting toxicity of such an OX40 antibody in an early clinical trial. The current phase 1 trials seem much more like phase 3 in scope. 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. For OX40 expression (Middle and Right), images represent OT-I + (Thy1. Study of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects With Moderate to Severe Atopic Dermatitis Brief description of study A Phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group study for subjects with moderate to severe AD whose disease cannot be adequately controlled with topical medications or for whom. Register today for the SITC 2018 Annual Meeting & Pre-Conference Programs!. OX40 functions on effector T cells to enhance their activity and proliferation. Opinions Split On Ox40. Moreover, the role of antibody-dependent cell-mediated cytotoxicity in depleting Tregs in addition to GITR agonism will be interrogated by 2 humanized IgG1 aGITR mAbs both of which engage Fc receptors and went into phase I trials in 2016 (INCAGN01876, NCT02697591 and MEDI1873, NCT02583165). TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. IBI307 is an anti-RANKL antibody under development for the treatment of osteoporosis and lytic bone lesions associated with cancer metastasis. ABBV-368 is an agonistic anti-OX40 monoclonal antibody that is being investigated in a Phase 1 clinical trial for solid tumors. In addition, Innovent is the first Chinese biopharmaceutical company to receive clinical trial approval from US FDA for an anti-OX40 monoclonal antibody. BINDING ANTAGONISTS. Tumor necrosis factor receptor superfamily member 4 (TNFRSF4) is also known as ACT35 antigen, OX40L receptor, TAX transcriptionally-activated glycoprotein 1 receptor, CD antigen CD134, OX40. Clinical Trial Finds Diet Works for Depression Pioneering new study suggests healthy food can be a powerful antidepressant. The IUPHAR/BPS Guide to Pharmacology. 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. TheraMAB starts oncology clinical program with its mAb targeting an immune checkpoint Tumor cells use various strategies to avoid immune reactions. These antibodies modify regulatory checkpoints of the immune system, and are able to increase the body's immune response to cancer. Hence, as these immune-enhancing antibodies are evaluated in human clinical trials there will likely be several used to augment tumor immunity (e. PF-04518600 targets OX40, a receptor found on the surface of a type of specialized immune cells called memory T-cells that have already been exposed to cancer antigens (substances that trigger an immune response). monoclonal antibody listed as MAB approval to initiate the US phase I clinical trial of its Anti-OX40 Monoclonal Antibody IBI101 in. Radiation therapy uses high-energy rays to kill tumor cells and shrink tumors. either alone or in combination with antibody-based OX40 stimulation. TNFRSF4 is receptor for TNFSF4 / OX40L / GP34 and can interacts with TRAF2, TRAF3 and TRAF5. OX40 / TNFRSF4 contains four TNFR-Cys repeats. One of the goals of the planned clinical trial is to assess the safety of the combination. Innovent Biologics, Inc. OX40 OX40 Effects of OX40 antibodies (1) Activated T cells removed selectively through ADCC activity Effects of OX40 antibodies (2) Post‐activation survival suppressed and clonal expansion/memory formation inhibited by blocking OX40 signaling High efficacy can be expected based on powerful inhibition of. 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. The binding prompts OX40 to help the T-cells survive and multiply. NCT02318394). They are conducting some of the largest phase 1 trials currently underway in cancer using these antibodies. 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. The antibody had a half-life of 27 to 37 days, with dose-related exposure in blood and a CSF-to-blood ratio of 0. IGM Biosciences Initiates First-in-Human Phase 1 Clinical Trial of IGM-2323 for the Treatment of Relapsed/Refractory B Cell Non-Hodgkin’s Lymphoma October, 2019 Read More. Arthritis Rheum 12 : 16811690, 1993. TLR9 agonists and anti-OX40 antibodies are currently under clinical development for cancer treatment. OX40 Like CD137, OX40 is a co-stimulatory molecule expressed. 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. Triggering OX40 signaling has been demonstrated in various mouse tumor models [10-14] as a potential antitumor therapy and its translation to clinical trials is under investigation [8,15]. However, it is not clear what IgG isotypes would be optimal for agonist antibodies that are required to activate co-stimulatory targets such as CD40, OX40, CD27, CD137, GITR, ICOS and HVEM. The concurrent treatment of mice-bearing tumors that are refractory to. Recombinant HEK 293T cells stably expressing an exogenous human OX40 (CD134) gene for drug screening and biological assays. These collections are currently recommended for research applications like FACS, functional assays, ELISA, Immunohistochemistry and Western Blot, and some are in the process of being validated for in vivo use. "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. It binds with OX40, a receptor on the surface of specialized immune T-cells that fight invaders. CpG and anti-OX40 are both already being studied in clinical trials. CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). Pre-clinical data confirms that IBI101 has a clear mechanism of action that enhances the activation of effector T cells and mediates the clearance of regulatory T cells, thus inhibiting the growth of tumor cells. The clinical trials on this list are studying Anti-OX40 Monoclonal Antibody. The immune stimulating properties of OX40 agonists could provide an immunologic stimulus to overcome some of the immunosuppressive properties of cancer, and thus. 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). We're all going to have to get familiar with that sort of talk, so here's what's going on: OX40, for its part, is a sort of second-wind system for activated T cells. Clinical Trials. to expansion, deactivation, or cell death depending on the local milieu. Agenus Announces Commencement of Phase 1/2 Clinical Trial of anti-OX40 Checkpoint Antibody INCAGN1949 in Patients with Solid Tumors - Third antibody from Agenus to enter the clinic this year. Agenus and Incyte will share all costs and profits for the GITR and OX40 antibody programs on a 50:50 basis, with Agenus eligible for potential milestones; TIM-3 and LAG-3 are royalty-bearing programs to be funded by Incyte, with Agenus eligible for potential milestones and royalties. View information about oncology clinical trials currently underway for the Genentech BioOncology pipeline of investigational molecules. Signaling pathways downstream of OX40 14 Figure 4. BINDING ANTAGONISTS. a phase I clinical trial is evaluating Venclexta in combination with Gazyva for. Brief description of study. Notably, an anti-OX40 monoclonal antibody (KHK4083) has been administered to patients with PS in a phase I clinical trial with improved effects. - Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTL4 antibody or any other antibody or drug targeting T-cell costimulation or checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc. 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. 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. Our data suggest that the anti-OX40 antibody should be administered at the same time as CpG or somewhat delayed but not the other way around. Today, MedImmune is investing in further development of OX40, and along with Providence and AgonOX, is expanding clinical trials for patients with melanoma, breast cancer, and prostate cancer. 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. • MOXR0916 is a humanized IgG1 monoclonal antibody drug candidate that targets OX40, and currently is being tested in a Phase I clinical trial • MOXR0916 functions as an agonist antibody, which results in activation rather than blockade, of the OX40 signaling pathway upon receptor binding. Our INCAGN1949 antibody targeting OX40 is part of our global alliance with Incyte. Kymab Announces Promising Results from Initial Clinical Study of New Antibody KY1005 for Treatment of Autoimmune Diseases Top-line Phase I data demonstrated. Given that OX40 triggering can potently stimulate T cells and potentially block/eliminate regulatory T cells, OX40 agonists have been investigated in multiple preclinical tumor models and anti-human OX40 monoclonal antibodies are currently being evaluated in clinical trials. cDNA clones were isolated from an expression library using the MRC OX40 mAb and the protein sequence for the OX40 antigen deduced. Anti-OX40 antibody is also currently being studied in phase 1 clinical trials (NCT02559024, NCT01644968, NCT02221960, NCT02318394, NCT02274155, NCT01862900, NCT01303705, and NCT02205333). 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. Materials and Methods Clinical trial ID#NCT01644968 Clinical trial was designed and performed as described in Supplementary Materials and Methods. PD-1 Axis Binding Antagonists. OX40 antibody treatment was well tolerated with. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. 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. Monsour, 2 Xiaolong Zhang, 1 Yongwon Choi, 3 Yaling Dou, 1 Naoto Ishii, 4 Rafik M. The MedImmune agents include the CTLA-4 blocking antibody tremelimumab, an OX40 receptor agonist antibody, and a B7-H1 (or PD-L1) blocking antibody. "OX40 signaling leads to PD-L1 induction via IFN-γ-upregulation. 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 provide the rationale for testing these agents clinically, injected locally in low doses to induce therapeutic anti-cancer immunity. Clinical trials are in progress for OX40-targeted therapy. OX40 (CD134), a membrane-bound member of the tumor-necrosis-factor-receptor superfamily, is expressed primarily on activated CD4 + T cells. Read the study abstract. Immune modulation with checkpoint inhibitor antibodies targeting GITR or OX40 to improve cancer immune therapy with DepoVaxTM vaccine and metronomic cyclophosphamide Immunovaccine Inc. Recombinant HEK 293T cells stably expressing an exogenous human OX40 (CD134) gene for drug screening and biological assays. Bloomberg the Company & Its Products Bloomberg Anywhere Remote Login Bloomberg Anywhere Login Bloomberg Terminal Demo Request. Rapid Screening of Anti-OX40 Antibodies for Cancer Immunotherapy. GBR 500 has been licensed to Sanofi and is in Phase 2 clinical trials in the US. Platform for rapid discovery and optimization of fully-human antibodies against a wide array of molecular targets – Six lead checkpoint programs. A phase I clinical trial has shown that administration of anti-OX40 antibody increased the acti- anti-OX40 mAb was well tolerated and induced prolifera- vation status of the CD8+ T cells as measured by the tion of CD8 and CD4 non-Treg cells in the peripheral co-expression of CD38 and HLA-DR on the cycling cells. The OX40–OX40L protein–protein interaction (PPI) is an important cell‐surface signalling co‐stimulatory regulator within the TNFR superfamily (TNFRSF) and a promising therapeutic target for immunomodulation. antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. With a legacy of putting patients first, Weill Cornell Medicine is committed to providing exemplary and individualized clinical care, making groundbreaking biomedical discoveries, and educating generations of exceptional doctors and scientists. Just a couple of years ago Ox40 was billed as one of the most promising targets in a new wave of immuno-oncology projects. 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. 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. (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. “OX40 signaling leads to PD-L1 induction via IFN-γ-upregulation. Acknowledgments TT MacDonald is a consultant to Cantab Pharmaceuticals. Recombinant HEK 293T cells stably expressing an exogenous human OX40 gene for drug screening and biological assays. 5 fold proliferation increase. 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). a phase I clinical trial is evaluating Venclexta in combination with Gazyva for. "We generated preclinical data demonstrating the efficacy of the antibody," Toniatti says. Shattuck Labs, Inc. STRATOS 1 & 2: considerations in clinical trial design for a fully human monoclonal antibody in severe asthma Clinical Trial Protocol [45]. Anaphylaxis caused by the GITR agonist antibody DTA-1 is dependent on GITR, IL-4, basophils, and platelet-activating factor. Blocking antibodies such as nivolumab and pembrolizumab were successfully developed in the clinic as IgG4 molecules. Mechanism 1: OX40 Forward Signaling in T Cells. Innovent Biologics, Inc. In this review, we discuss the recent advances and clinical promise of agonistic anti-CD137 monoclonal antibody therapy. About this Clinical Trial. The program is funded by Incyte with Agenus eligible for potential milestones and 15% royalties, subject to reduction for certain third party obligations. The double knock-in model has both humanized PD-1 and OX40 receptors within a functional mouse immune system. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. Here, we extend our observations to mammary carcinomas from mice of different genetic background. 45 Since OX40 lacks the YMXM PI3K binding site of CD28 and ICOS, it is not clear whether OX40 activates PI3K directly or indirectly. KY1005 is an antagonist of OX40-Ligand (OX40L) with the potential to treat a number of autoimmune diseases. Immunotherapy with monoclonal antibodies, such as avelumab, utomilumab, and anti-OX40 antibody PF-04518600, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Home News Incyte Takes on Global Responsibility for Agenus' GITR and OX40 Antibody Immuno-oncology firm Agenus started the Phase I/II clinical trial with INCAGN1949 in patients with solid. Your Message Will Go To Rachel Greenstein 650-723-2312. 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. m "Worldwide clinical research on anti-OX40 antibodies is limited. The researchers started by exploring dual combination immunotherapy. TIL express TNFR molecules but the endogenous ligand is often limited. 31 in Science Translational Medicine. 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. Promising results were observed, showing a strong bioactivity of the compound, although no antitumor responses. A phase I clinical trial using a mouse mAb that agonizes human OX40 in advanced cancer patients reported an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. The efficacy and toxicity of combining anti-OX40 therapy with either CTLA-4 or PD-1 has not been evaluated in humans, although Phase 1 clinical trials for both combinations are currently accruing patients (NCT02205333). 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. Experimental Design: We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade. 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. 3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. 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. Fox and team are about to initiate a clinical trial in which women with triple-negative breast cancer will receive a vaccine (to prime patients' T cells and upregulate OX40 receptors) prior to receiving anti-OX40 therapy; the patients will then be randomly assigned to anti-PD1 or not after anti-OX40 administration. An agonistic, humanized monoclonal antibody against receptor OX40 (CD134), with potential immunostimulatory activity. The OX-86 monoclonal antibody reacts with mouse OX-40 also known as CD134. School of Medicine in the US are this month starting a clinical trial using human patients. NCT02318394). Kymab's therapeutic antibody KY1005 has successfully completed dosing of the 24th subject in its first clinical study. 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. Clinical Trials Ongoing Including Combination Therapy. NCI's basic information about clinical trials explains the types and phases of trials and how they are carried out. It is monoclonal antibody. Our results provide the rationale for testing these agents clinically, injected locally in low doses to induce therapeutic anti-cancer immunity. CD137, or 4-1BB, is a tumor necrotic factor receptor found primarily on activated T cells, natural killer (NK) cells, and myeloid cells. OX40/OX40L is a pair of important positive costimulatory signal molecules in the second signal system of T cells. Sturgill, PhD, and William L. of antibodies which affect T cell regulation by targeting a diversity of coinhibitory and costimulatory molecules. We look forward to learning more about SL-279252 in the clinic and expect to gain insight into whether it can improve upon antibody-based PD-1. Innovent Biologics, Inc. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas. 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. Both reagents have already been tested in clinical trials as single agents and were well tolerated. 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.