Mosunetuzumab genentech

More than 50 bispecific antibodies are in oncology clinical development with a large diversity in formats, directed at a range of immune and tumor targets. Bispecifics have demonstrated the potential for enhanced efficacy and reduced systemic toxicity. However, they are complex modalities with challenges to overcome in early clinical trials, including selection of relevant starting doses and dose escalation strategy due to non-intuitive exposure-response relationships.

In this context, prediction and management of cytokine-release syndrome CRS is important. Multiple factors can contribute to between-patient variability, including tumor type, avidity, receptor expression, effector-to-target-cell fill convex hull opencv, and presence of soluble target.

Mechanistic, quantitative systems pharmacology QSP models are increasingly being used in the design of bispecifics and to guide translation research, clinical trial design, dose regimen optimization, and patient selection. With over 20 years of experience working in the pharmaceutical industry at Sanofi and Pfizer, Piet brings considerable skill and experience to QSP projects and contributes to the strategic development of Certara.

Chi has 13 years in clinical drug development experience and specializes in quantitative clinical pharmacology of small molecule pharmaceuticals and biologics. Featured Product. Simcyp: 20 Years of Innovation. Contact Investors Careers Support. Wed, January 20th. Contact Us.Bispecific antibodies have two arms.

One arm of the drug attaches to a specific protein on the lymphoma cell. The other arm activates immune cells in the patient to kill the lymphoma cells. Several bispecific antibodies are in development for the treatment of non-Hodgkin lymphoma NHL. Bispecifics appear capable of inducing complete remissions in patients with refractory or resistant NHL including patients that have failed multiple therapies, stem cell transplantation or CAR T cell therapy.

The clinical trial has evaluated over patients with refractory or resistant NHL, including patients who had relapsed following, or are resistant to CAR T-cell therapy. Single-agent mosunetuzumab was effective and well tolerated as first-line treatment for elderly and unfit patients with diffuse large B-cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.

Researchers assessed mosunetuzumab among patients with untreated DLBCL or high-grade B-cell lymphomas who were not eligible to receive standard chemo-immunotherapy because they were at least 80 years old or had a comorbidity that made them unable to tolerate a full dose of chemo-immunotherapy. Treatment-related side effects were minimal and were mostly related to cytokine release syndrome and infusion reactions, with rare fatigue and gastrointestinal adverse events. No fatal side effects were reported.

Six patients experienced cytokine release syndrome, all which resolved within days. Mosunetuzumab is currently only available in ongoing clinical trials and must still undergo approval by the FDA. Patients with resistant or refractory NHL may want to follow its development as it appears to represent a significant treatment advance.

For individuals achieving a complete response, responses were durable and persisted for as long as 21 months at the time of the report. In November Regeneron paused new enrollment of patients with B-cell non-Hodgkin lymphomas in compliance with a U. Subcutaneous administration distinguishes epcoritamab from competing therapies in the class. Besides being more convenient and less time consuming, subcutaneous administration leads to more gradual increases in plasma cytokine levels and lower peak levels, Hutchings explained, noting that potency studies showed T cell-mediated killing at low levels of CD20 expression.

In Follicular lymphoma nine of 10 evaluable patients responded, including five CRs and two of four patients with mantle cell lymphoma responded to epcoritamab. Epcoritamab is being co-developed by Genmab and AbbVie. Hodgkins Lymphoma. Multiple Myeloma.

Myelodysplastic Syndrome. Neuroendocrine Tumors. Non Hodgkins Lymphoma. Triple Negative Breast. Weaver M. Several bispecific antibodies are in development for the treatment of non-Hodgkin lymphoma NHL Bispecifics appear capable of inducing complete remissions in patients with refractory or resistant NHL including patients that have failed multiple therapies, stem cell transplantation or CAR T cell therapy.

Breast Cancer Overviews. By Dr. Breast Cancer Treatment. Destiny Clinical Trials.By Caroline Helwick May 10, Advertisement. The bispecific T-cell engager blinatumomab was the first such agent to be approved by the U. Today, dozens of next-generation bispecific antibody constructs are in clinical trials, and they are poised to have a huge impact in the treatment of lymphoma and other hematologic malignancies, experts agreed.

Mosunetuzumab is an off-the-shelf product, requiring no time for manufacturing, and appears to work well even in patients with advanced non-Hodgkin lymphoma NHL whose disease progresses after treatment with chimeric antigen receptor CAR T-cell therapy. In the study presented at the ASH meeting, high response rates were achieved, with good tolerability.

It gets around the problem of the time it takes to generate CAR T cells. Brodsky said. Basem M. Bispecific antibodies recognize two different epitopes.

Having dual specificity, they can redirect T cells to tumor cells to enhance tumor killing, simultaneously block two different signaling pathways or mediators with unique or overlapping functions, interact with two different surface antigens, and deliver payloads to targeted sites. Their development was initially hampered by manufacturing difficulties, but newer constructs are more stable, easier to produce, and less immunogenic. Two bispecific antibodies have been FDA approved—blinatumomab and catumaxomab—but more than 30 are now in clinical trials, and two-thirds are anticancer agents.

The following studies presented at the ASH meeting demonstrate the potential of several of these newer drugs. Mosunetuzumab binds to CD20 on the surface of malignant B cells and to CD3 on the surface of cytotoxic T cells, resulting in crosslinking of the T-cell receptor and subsequent activation of an immunologic T-cell response.

In brief, patients with a poor prognosis were treated, many of whom had received CAR T-cell therapy previously.

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Schuster said. Adverse events leading to treatment withdrawal occurred in 5. Cytokine-release syndrome and neurologic toxicity were mostly limited to grade 1 and 2. Patients received 12 weekly intravenous doses of REGN, followed by everyweek dosing for 12 doses 36 weeks total.

Response was assessed for patients treated with at least 80 mg who had a week 12 scan. Bannerji reported. The median progression-free survival was Six patients discontinued treatment because of toxicity.

In both aggressive and indolent subsets, the baseline CD20 level did not predict response or nonresponse, but some disease progression may be associated with loss of CD20, Dr. Bannerji proposed. Programmed cell death ligand 1 PD-L1 expression and programmed cell death protein 1 PD-1 -positive tumor-infiltrating lymphocytes in malignant lymph node tissue were higher after REGN treatment.

Bannerji said. GEN promotes T-cell activation and expansion, induces rapid T-cell—mediated killing of CDpositive cells dependent on simultaneous binding of CD3 and CD20and retains activity in the presence of CD20 monoclonal antibodies, she said.The two investigational agents, mosunetuzumab and glofitamab, are designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells.

The two agents differ in their structures but are designed to maximize potential clinical benefits for patients. The drug binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells.

Polatuzumab vedotin is an antibody-drug conjugate or ADCs, a highly targeted biopharmaceutical drug that combines monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.

With ten approved drugs on the market, ADCs have become a powerful class of therapeutic agents in oncology and hematology. Limited treatment options While approximatelypeople worldwide are diagnosed with NHL each year, treatment options are currently limited and resistance to existing therapies or relapse following treatment is common.

Pivotal data for these medicines are expected this year and Genentech is targeting a regulatory filing for mosunetuzumab in FL by the end offollowing its U. Key data on mosunetuzumab and glofitamab to be presented at the meeting include:. Key data at the meeting include:. Last accessed on June 4, Abstract J Clin Oncol 39, suppl 15; abstr Sign in.

Forgot your password? Get help. Password recovery. Advertisement 1. Advertisement 3. Advertisement 5. Advertisment D - December 19, Eric T. Rosenthal - October 9, Peter Hofland, Ph. D - November 30, All Rights Reserved.Blood ; Supplement 1 : Methods: Pts received mosunetuzumab intravenously IV as follows: Group A, mosunetuzumab administered on day D 1 of each day cycle C ; and Group B, ascending doses of mosunetuzumab administered on D1, D8, and D15 of C1, then at a fixed dose on D1 of every day cycle thereafter, up to a maximum of 17 cycles.

Additional pts were enrolled to further characterize clinical activity at cleared dose levels. Primary outcome measures are maximum tolerated dose MTD based on dose-limiting toxicities DLTstolerability, pharmacokinetics PKand best objective response.

The median duration of treatment was 81 days range days in Group A and 68 days range days in Group B. Doses up to 2. The MTD has not yet been reached in either group. Safety was similar in both groups even with higher dose levels tested in Group B Table 2. The majority of treatment-emergent AEs occurred during Cycle 1.

All cases of CRS were grade per Lee et al. Blood grading criteria. One case of febrile neutropenia was reported assessed as unrelated to study drug ; no neutropenia-related infections were reported. One fatality from hemophagocytic lymphohistiocytosis in a pt with suspected chronic active Epstein-Barr virus infection was attributed to study treatment and one pt died of hepatic failure 26 days after the first dose; considered possibly related to treatment.

Mosunetuzumab displayed a half-life of days. CRs appear durable, with all pts achieving a CR remaining in remission median follow-up days, range days. The safety profile, with MTD not yet reached and with most AEs being low-grade and manageable, appears favorable compared to current standard anti-lymphoma therapies including T-cell directed agents.

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Positive trials results showing a significant improvement in survival boost Roche’s Polivy

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Close Abstract. Article Navigation.All rights reserved. Mosunetuzumab, a novel bispecific antibody, generated durable responses in patients with highly refractory non-Hodgkin lymphomas, including complete remissions in Mosunetuzumab, a novel bispecific antibody, generated durable responses in patients with highly refractory non-Hodgkin lymphomas NHLsincluding complete remissions CRs in The agent represents a promising therapy for patients whose disease has recurred after receiving CAR therapy or is progressing too rapidly to be treated with personalized gene therapy, said lead investigator Stephen J.

Schuster, MD. Mosunetuzumab is a humanized antibody that contains 2 antigen-recognition sites: CD3, a T-cell surface antigen, and CD20, a tumor-associated antigen exclusively expressed on B cells. Although CAR agents represent a significant advance in treating refractory B-cell malignancies, Schuster said, two-thirds of patients with lymphomas do not respond.

He also said the process of producing and obtaining insurance approval for CAR therapy delays treatment by several weeks. The data are from Group B of the study, in which patients received mosunetuzumab intravenously with stepped-up dosing on days 1, 8, and 15 of cycle 1, and then as a fixed dose on day 1 of each subsequent day cycle maximum 17 cycles.

After a median follow-up of 6 months, 17 patients remain in CR. Twenty-four patients remain in CR up to 26 months after initial treatment. Notably, patients who previously received CAR T-cell therapy also responded to mosunetuzumab. Among 18 evaluable patients in this cohort, the ORR was The patient achieved a CR after 3 cycles of mosunetuzumab therapy and remains in CR after more than 8 months.

Three-quarters of the remission patients are off therapy. In the population evaluable for safety, the study has enrolled patients; the median age is The safety population comprises The median number of prior system therapies was 3 range, In terms of prior therapies, Of 30 patients who had received prior CAR T-cell therapy, 22 This group had received a median 5 lines of prior systemic therapies range, In the safety analysis, the incidence of all grades of CRS was The majority of these events were of grade 1 or 2 severity, occurred mostly in cycle 1 of therapy, and had a median duration of 2 days range, There were 3 grade 3 CRS occurrences in the total call ui apk 1.For the safety of our patients and staff, we have updated our visitor policy, effective December Read the latest information for visitors.

The purpose of this study is to find the highest dose of the investigational drug BTCTA that can be given safely in patients with B-cell non-Hodgkin lymphoma NHL or chronic lymphocytic leukemia CLL that has continued to grow or came back despite prior treatment.

BTCTA is a form of immunotherapy. It attaches to cancerous B cells and normal T cells in the immune system. BTCTA is designed to trigger an immune response against cancer cells by directing T cells to kill cancerous B cells. It is given intravenously by vein. To be eligible for this study, patients must meet several criteria, including but not limited to the following:.

For more information about this study and to inquire about eligibility, please contact Dr. Matthew Matasar at Skip to main content Important Update to Visitor Policy.

Eligibility To be eligible for this study, patients must meet several criteria, including but not limited to the following: Patients must have CDpositive B-cell NHL or CLL that has come back or continued to grow despite prior treatment. Patients must recover from the serious side effects of previous therapies before entering the study.

Patients must be physically well enough that they are fully ambulatory, capable of all self care, and are capable of all but physically strenuous activities.

As an example, patients must be well enough that they would be able to carry out office work or light housework. This study is for patients age 18 and older.

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Protocol Investigator Matthew J. Co-Investigators Lorenzo Falchi. Memorial Sloan Kettering Commack. Memorial Sloan Kettering Westchester. At MSK, we focus exclusively on cancer. The MSK difference. Our network of regional centers brings our expert care closer to you. Explore locations.

Explore our doctors. Learn about Mosunetuzumab (RG), an investigational T-cell bispecific antibody. Learn about the clinical developments today. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two 'Fab' regions, but is different from naturally. Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory (R/R) follicular lymphoma (FL), a. Mosunetuzumab is a fully humanised, full-length, IgG1 bispecific antibody targeting CD20 antigen and CD3 antigen, being developed by Genentech, a subsidiary.

Results to be presented for the first time show mosunetuzumab induces Genentech plans to submit the new data to the U.S. Food and Drug. ATLANTA — An experimental bi-specific T-cell engaging antibody, mosunetuzumab (Genentech), has induced high response rates and long-duration.

were free of disease-related complications and did not require further treatment 1 year after receiving mosunetuzumab (Genentech). Genentech: Phase I/II Result Shows Mosunetuzumab Induces Complete Response Rates In Blood Cancer.

Contributor. RTTNews. Purev:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Vallurupalli:Received Research funding to. Roche said it has recently submitted the initial marketing application for mosunetuzumab to the European Medicines Agency.

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Subsidiary Genentech. Genentech, Inc., South San Francisco, CA, United States; 17Product Background: Mosunetuzumab is a novel CD20/CD3 bispecific anti. If approved, mosunetuzumab has the potential to be a first-in-class Genentech is an equal opportunity employer, and we embrace the increasingly diverse.

Roche/Genentech, Kite/Gilead, Novartis, BeiGene · Merck, Amgen, MustangBio, AstraZeneca · CCR4 CAR T cells for treatment of patients with CCR Roche-Genentech reported promising results from its single-arm study of the bispecific monoclonal antibody mosunetuzumab in patients. (RTTNews) - Genentech, a member of the Roche Group (RHHBY), data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab.

9Genentech, Inc., South San Francisco, CA Mosunetuzumab (Mosun) is a full-length, fully humanized IgG1 CD20/CD3 bispecific antibody that. Genentech is doing amazing things in the life science space. If you are looking to grow your company to this stage, leasing with Excedr could help make. Based on the findings, drug maker Genentech announced it will file for FDA approval for mosunetuzumab to treat this form of non-Hodgkin. Drug maker Genentech announced it will f bispecific T-cell engaging antibody mosunetuzumab demonstrated high response rates.

Roche's Genentech is looking to drive a lead bispecific antibody Roche's mosunetuzumab, a bispecific targeting the CD20 protein on.