Epcoritamab + Rituximab + Lenalidomide for Lymphoma
(EPCORE™FL-2 Trial)
Recruiting in Palo Alto (17 mi)
+206 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Genmab
Disqualifiers: Major surgery, Active CMV, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests a new drug combination for adults with untreated follicular lymphoma, a type of blood cancer. The new treatment includes epcoritamab, lenalidomide, and rituximab, which work together to help the immune system attack cancer cells. The study will check how safe and effective this combination is. Lenalidomide combined with rituximab has shown high efficacy in both relapsed/refractory and untreated follicular lymphoma.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop your current medications. It's best to discuss this with the study doctors to understand how your current medications might interact with the trial treatments.
What data supports the effectiveness of the drug combination Epcoritamab, Rituximab, and Lenalidomide for treating lymphoma?
Research shows that combining lenalidomide with rituximab can improve outcomes in patients with certain types of lymphoma, especially those who did not respond well to rituximab alone. This combination has been effective in prolonging the time patients live without their disease getting worse, particularly in follicular lymphoma.
12345Is the combination of Epcoritamab, Rituximab, and Lenalidomide safe for treating lymphoma?
Epcoritamab has been approved for certain types of lymphoma, indicating it has been deemed safe enough for use, though specific safety data for the combination with Rituximab and Lenalidomide is not detailed. Rituximab and Lenalidomide together have a known safety profile, with common side effects like low white blood cell counts and rashes, which are generally manageable.
45678How is the drug Epcoritamab + Rituximab + Lenalidomide unique for treating lymphoma?
This drug combination is unique because it includes Epcoritamab, a novel component that works alongside Rituximab and Lenalidomide to potentially enhance the immune system's ability to target and destroy lymphoma cells, offering a new approach compared to traditional chemotherapy.
12459Eligibility Criteria
Adults with previously untreated Follicular Lymphoma (FL) who need systemic treatment and meet specific medical criteria, including a certain stage of disease and tumor size. They must be able to follow the study procedures and have an acceptable performance status for daily activities.Inclusion Criteria
I need treatment for my condition as per my doctor's assessment.
My PET/CT scan shows active cancer spots.
I am eligible for standard cancer treatments like CIT or R2.
+16 more
Exclusion Criteria
I have not had major surgery in the last 4 weeks.
I am currently suffering from an active CMV infection.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive R2 (rituximab and lenalidomide) alone or in combination with epcoritamab, or investigator's choice chemoimmunotherapy for 120 weeks
120 weeks
Regular visits at a hospital or clinic
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 10 years
Participant Groups
The trial is testing the safety and effectiveness of Epcoritamab combined with Rituximab and Lenalidomide in treating FL. Participants are divided into groups receiving different treatments, including standard chemoimmunotherapy options, over a period of 120 weeks.
4Treatment groups
Experimental Treatment
Group I: Arm C: Lenalidomide and Rituximab (R2)Experimental Treatment2 Interventions
Participants will receive lenalidomide and rituximab (R2) during the 120 week treatment duration.
Group II: Arm B: Chemoimmunotherapy (CIT) Option BExperimental Treatment4 Interventions
Participants will receive CIT Option B (G and bendamustine (Benda) \[G-Benda\]/R-Benda during the 120 week treatment duration.
Group III: Arm B: Chemoimmunotherapy (CIT) Option AExperimental Treatment6 Interventions
Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) \[G-CHOP\]/ rituximab (R)-CHOP during the 120 week treatment duration.
Group IV: Arm A: Epcoritamab + Lenalidomide and Rituximab (R2)Experimental Treatment3 Interventions
Participants will receive epcoritamab in combination with R2 during the 120 week treatment duration.
Epcoritamab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Epkinly for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
- Diffuse large B-cell lymphoma after two or more lines of systemic therapy
🇪🇺 Approved in European Union as Tepkinly for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
- Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fort Wayne Medical Oncology and Hematology- South Office /ID# 259583Fort Wayne, IN
Cancer Specialists of North Florida /ID# 262445Jacksonville, FL
Advent Health /ID# 261578Orlando, FL
Illinois Cancer Care, PC /ID# 261526Peoria, IL
More Trial Locations
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Who Is Running the Clinical Trial?
GenmabLead Sponsor
AbbVieIndustry Sponsor
References
A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q- myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma. Perhaps most impressive is the efficacy of lenalidomide when combined with monoclonal antibodies. Impressive efficacy and toxicity profiles with the combination of lenalidomide and rituximab in B-cell lymphomas in both the upfront and relapsed/refractory setting may allow a shift in our current treatment paradigm in both indolent and aggressive non-Hodgkin lymphoma (NHL). This review will summarize the current data in the relapsed/refractory and front-line setting of NHL with single-agent lenalidomide as well as its use in combination with other agents.
Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]Lenalidomide (Revlimid®) is a targeted immunomodulatory drug with multiple mechanisms of action. In the USA and the EU, oral lenalidomide is indicated in combination with rituximab or a rituximab product for the treatment of patients with previously treated follicular lymphoma. In the pivotal, phase III AUGMENT trial, lenalidomide + rituximab significantly prolonged progression-free survival (PFS; primary endpoint) relative to placebo + rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma, with the PFS benefit appearing to be specific to patients with follicular lymphoma and extending to elderly patients with this subtype. Lenalidomide + rituximab also demonstrated activity in an interim analysis of the phase III MAGNIFY trial in patients with relapsed or refractory indolent non-Hodgkin lymphoma, including those with rituximab-refractory disease. Lenalidomide had an acceptable tolerability profile. Although grade 3 or 4 neutropenia occurred more frequently with lenalidomide + rituximab than with placebo + rituximab, this was generally well managed with dosage adjustments and growth factor support. In conclusion, lenalidomide in combination with rituximab represents an important new treatment option for previously treated follicular lymphoma, including patients whose disease has become refractory to rituximab.
The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]Recent advances in the treatment of patients with non-Hodgkin lymphoma have driven a paradigm shift from standard chemotherapy to an ever-expanding choice of targeted agents and combinations. As an orally bioavailable immunomodulator with antineoplastic, immunologic, and antiproliferative activity in B-cell lymphoma, lenalidomide has emerged as one such option. Lenalidomide demonstrates clinically significant activity with a favorable safety profile as a single agent, as well as in combination therapy. Herein, we review accumulated clinical data on lenalidomide, with particular reference to patients with first-line and relapsed/refractory mantle cell lymphoma, indolent lymphoma, and diffuse large B-cell lymphoma.
Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cell-mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 mAb. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy.
A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). [2023]This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL).
Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. [2021]Frontline treatment for patients with indolent non-Hodgkin lymphoma often includes immunochemotherapy. Although the disease of most patients responds to initial treatment, relapse is common. Recent results from the phase 3 Augment trial showed that combining rituximab with the immunomodulatory drug lenalidomide (R2) significantly improved efficacy over rituximab monotherapy in patients with recurrent non-Hodgkin lymphoma. As a result of these data, R2 was approved in the US (Food and Drug Administration) and Japan (Pharmaceuticals and Medical Devices Agency) for previously treated adult patients with follicular and marginal zone lymphoma; and by the European Medicine Agency and the Swiss Agency for Therapeutic Products (Swissmedic) for previously treated adult patients with follicular lymphoma. R2 has also been studied as initial treatment, where results have been comparable, but not superior, to chemoimmunotherapy. The resulting expanded use of R2 reinforces the need for a detailed review of its safety profile and management, as presented here. Tolerability of R2 has been consistent among trials, with most adverse events (AEs) being predictable and manageable. Hematologic AEs, particularly grade 3/4 neutropenia; low-grade cutaneous reactions, such as rash; and gastrointestinal AEs represent the most common AEs associated with R2. The general R2 safety profile and optimal strategies for AE management are discussed.
Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.
Epcoritamab: First Approval. [2023]Epcoritamab (epcoritamab-bysp; Epkinly™; Tepkinly®) is a subcutaneously administered CD3×CD20 T-cell-engaging bispecific antibody being co-developed by Genmab and AbbVie for the treatment of mature B-cell non-Hodgkin lymphoma subtypes (B-NHLs), including diffuse large B-cell lymphoma (DLBCL). Epcoritamab received its first (conditional) approval on 19 May 2023, in the USA, for the treatment of adult patients with relapsed or refractory (R/R) DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥ 2 lines of systemic therapy. Elsewhere, epcoritamab has received a positive opinion in the EU as a monotherapy for the treatment of adults with R/R DLBCL after ≥ 2 lines of systemic therapy, and is currently under regulatory review in Japan for the treatment of adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy. Clinical development of epcoritamab as monotherapy and in combination with standard of care agents for the treatment of mature B-NHLs is ongoing globally. This article summarizes the milestones in the development of epcoritamab leading to this first approval for R/R DLBCL.
Lenalidomide in follicular lymphoma. [2021]Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.