Tazemetostat + Mosunetuzumab for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
Overseen bySamuel Yamshon, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Weill Medical College of Cornell University
Disqualifiers: Grade 3b FL, Myeloid malignancies, CNS lymphoma, Autoimmune disease, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The goal of this study is to learn about the safety and effectiveness of the combination of tazemetostat pills in combination with mosunetuzumab injections for people with follicular lymphoma who haven't received treatment before. The investigators hypothesize that tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product without compromising the safety.
Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously treated follicular lymphoma and currently undergoing study in other lymphomas.
Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends: one attaches to T cells in the immune system and the other attaches to lymphoma cells, helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is approved by the FDA to be given intravenously (directly into a vein) but is not yet approved by the FDA is not yet approved as an injection under the skin, which is how it is given in this study. They have not yet been studied in combination.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What makes the drug combination of Tazemetostat and Mosunetuzumab unique for treating follicular lymphoma?
This drug combination is unique because it combines Mosunetuzumab, a bispecific antibody that engages T-cells to target cancer cells, with Tazemetostat, an oral inhibitor that targets a specific mutation in some follicular lymphoma cases. This approach offers a novel mechanism by combining immunotherapy with targeted therapy, potentially improving outcomes for patients who have not responded to other treatments.
12345Eligibility Criteria
This trial is for adults with untreated follicular lymphoma (Grades 1-3a) who can follow the study plan and are willing to use effective birth control. People with a history of certain blood cancers, severe infections like Hepatitis B/C or HIV, significant heart or lung disease, recent major surgery, CNS diseases, pregnancy, organ transplants, allergic reactions to monoclonal antibodies or active autoimmune diseases cannot join.Inclusion Criteria
Ability to comply with the study protocol
Willing to use highly effective contraception, if of childbearing potential
I have not had any drug treatments for lymphoma, only local radiation if any.
+1 more
Exclusion Criteria
My slow-growing lymphoma has changed into a more aggressive type.
I have or had brain lymphoma or cancer spread to the lining of my brain and spinal cord.
I have had an organ transplant.
+20 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive subcutaneous mosunetuzumab and oral tazemetostat in 28-day cycles for up to 12 cycles
48 weeks
12 visits (in-person)
Response Assessment
Response assessments by PET/CT at 12 weeks, 30 weeks, and 48 weeks for ongoing response
48 weeks
3 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
1 visit (in-person)
Participant Groups
The trial tests tazemetostat pills combined with mosunetuzumab injections in patients who haven't had prior treatments for follicular lymphoma. Tazemetostat targets an enzyme linked to lymphoma growth while mosunetuzumab directs the immune system against cancer cells. Their combination effectiveness and safety are under evaluation.
1Treatment groups
Experimental Treatment
Group I: Subcutaneous Mosunetuzumab and Oral TazemetostatExperimental Treatment2 Interventions
50 patients will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation.
Mosunetuzumab is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
🇺🇸 Approved in United States as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Weill Cornell Medicine/NewYork-Presbyterian HospitalNew York, NY
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
Genentech, Inc.Industry Sponsor
Epizyme, Inc.Industry Sponsor
References
Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. [2022]Mosunetuzumab is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumour activity of fixed-duration mosunetuzumab in patients with relapsed or refractory follicular lymphoma who had received two or more previous therapies.
Positive Results for Tazemetostat in Follicular Lymphoma. [2019]A recently reported clinical trial indicates that the EZH2 inhibitor tazemetostat is effective against relapsed or refractory follicular lymphoma. Three of 28 patients with EZH2 mutations had complete responses, and 17 had partial responses.
The role of tazemetostat in relapsed/refractory follicular lymphoma. [2021]Large strides have been made in the treatment of follicular lymphoma (FL) over the last few years. Although the majority of patients respond to upfront therapy, many experience disease progression with a progressive shortening of subsequent treatment free intervals. New treatment options are therefore crucial for such patients. Tazemetostat is a first-in-class, selective, oral inhibitor of enhancer of zester homolog 2 (EZH2), a histone methyltransferase that is mutated in about a quarter of FL cases. Tazemetostat was recently approved for the treatment of patients with relapsed FL after 2 or more prior lines of therapy in the presence of an EZH2 mutation and for those without any other available therapeutic option, independently of EZH2 mutation status. In this review, we will summarize the background and key data that led to the development of tazemetostat, and, ultimately, to its approval for this indication.
Mosunetuzumab: First Approval. [2022]Mosunetuzumab (Lunsumio®), an anti-CD20/CD3 T-cell engaging bispecific antibody, is being developed by Roche for the treatment of relapsed or refractory follicular lymphoma. Mosunetuzumab was recently conditionally approved in the EU for the treatment of relapsed or refractory follicular lymphoma in adults who have received at least two prior systemic therapies. This article summarizes the milestones in the development of mosunetuzumab leading to this first approval for relapsed or refractory follicular lymphoma.
Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]Bispecific antibodies are emerging as a promising new immunotherapy modality and are actively being evaluated in clinical trials for patients with lymphoma. As the first BsAb to receive regulatory approval for lymphoma, mosunetuzumab, an antiCD20/anti-CD3 BsAb, is an exciting new option for patients with relapsed or refractory (R/R) follicular lymphoma. The approval was based on results from an international, multicenter, phase 2 trial in patients with relapsed or refractory (R/R) follicular lymphoma following at least 2 prior lines of systemic therapy. Mosunetuzumab demonstrated remarkable efficacy with an overall response rate of 80% and complete response rate of 60%. Here we provided an overview of the latest clinical data on mosunetuzumab in lymphoma presented at the 2022 ASH Annual Meeting.