Epcoritamab for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
Overseen byGottfried Von Keudell, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Beth Israel Deaconess Medical Center
Must be taking: Antivirals
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Cardiac conditions, Neurologic conditions, CNS involvement, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This research is being done to see if epcoritamab is effective in treating follicular lymphoma as a second line of treatment.
The name of the study drug in this research study is:
-Epcoritamab (a type of antibody)
Do I need to stop my current medications to join the trial?
The trial requires that you stop any prior anti-lymphoma therapy at least 4 weeks before starting epcoritamab. If you are on immunosuppressive therapy for non-lymphoma-related reasons, you must stop it 28 days before starting the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Epcoritamab for treating follicular lymphoma?
Research shows that Epcoritamab, a drug that helps the body's immune cells target and kill cancer cells, has shown strong anti-tumor activity in patients with follicular lymphoma, even if they have had previous treatments. In studies, it effectively killed cancer cells in a significant number of patients with this type of lymphoma.
12345How is the drug Epcoritamab unique for treating follicular lymphoma?
Epcoritamab is unique because it is a bispecific antibody that engages T-cells to target and kill cancerous B-cells, and it is administered subcutaneously (under the skin), which is different from many other treatments that are given intravenously (through a vein). This drug has shown strong anti-tumor activity even in patients who have previously been treated with other CD20-targeted therapies.
12356Eligibility Criteria
This trial is for adults with follicular lymphoma who didn't fully respond to initial treatment. They should have a life expectancy over 2 years, good organ function, and no recent severe illnesses or drug abuse. Participants must not be pregnant, agree to use birth control, and have had only one prior therapy.Inclusion Criteria
Agreement not to donate eggs (ova, oocytes) or sperm for assisted reproduction during and after the trial
My cancer has either shrunk or not grown after initial treatment.
Life expectancy of greater than 2 years
+14 more
Exclusion Criteria
Current alcohol or drug abuse, psychiatric illness, or unstable social situation
I have not been hospitalized for an infection in the last 4 weeks.
History of allergic reactions to compounds similar to epcoritamab
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive Epcoritamab for up to 12 cycles, with varying frequency of administration
12 months
Frequent visits during cycles 1-3, less frequent in later cycles
Follow-up
Participants are monitored for safety and effectiveness every 3 months for 2 years or until disease worsens
24 months
Every 3 months
Long-term Follow-up
Participants are monitored for overall survival and progression-free survival up to 5 years
Up to 5 years
Participant Groups
The study tests Epcoritamab as a second-line treatment for follicular lymphoma. It's an antibody that targets the cancer cells. Patients will receive this medication to see if it can improve their condition after other treatments haven't led to complete remission.
1Treatment groups
Experimental Treatment
Group I: EpcoritamabExperimental Treatment1 Intervention
35 participants will be enrolled and will complete study procedures as follows:
* Baseline visit with imaging (CT, MRI or PET scan) and bone marrow biopsy.
* Imaging after Cycles 3 and 6 only.
* Cycles 1-3:
--Days 1, 8, 15 and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily
* Cycles 4-9:
--Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily
* Cycles 10-12:
--Day 1 of 28 day cycles: Predetermined dose of Epcoritamab 1x daily
* End of Treatment visit with imaging and bone marrow biopsy.
* Follow up: every 3 months for 2 years or until disease worsens.
* Off study visit with imaging.
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:
Beth Israel Deaconess Medical CenterBoston, MA
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Who Is Running the Clinical Trial?
Beth Israel Deaconess Medical CenterLead Sponsor
GenmabIndustry Sponsor
References
Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. [2021]Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20+ tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (n = 16), follicular lymphoma (n = 15), and mantle cell lymphoma (n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.
Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. [2021]Patients with relapsed or refractory B-cell non-Hodgkin lymphoma have few treatment options. We aimed to establish the safety and recommended phase 2 dose of epcoritamab, a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells.
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.
Novel treatment approaches and future perspectives in follicular lymphoma. [2020]Follicular lymphoma (FL) is a common B-cell malignancy characterized by relatively indolent growth and incurability with an expected lifetime course of serial intermittent treatment courses. Many patients with FL have lives shortened by the disease and despite a relatively favorable prognosis relative to other incurable systemic malignancies, optimal management of FL has not been achieved. This review focuses on identifying both patients for whom novel therapies might be most beneficial as well as systematically reviewing novel strategies at various levels of investigation. Prognostic markers incorporating clinical measurements and tumor genetics are discussed, yet at the time of diagnosis do not yet powerfully discriminate patients for whom specific strategies are beneficial. Reassessment of prognosis after evaluating the response to initial therapy is the most powerful identifier of those in need of novel management strategies. For initial therapy of high burden systemic disease, anti-CD20 antibody along with chemotherapy or immunomodulators all offer relatively similar effects on overall survival with subtly different effects on progression-free survival and quality of life. Several new agents currently under investigation in the upfront setting are discussed. Perhaps the best testing ground for novel therapies is in patients with early relapse following initial immunochemotherapy. Ongoing research in multiple therapy classes including, novel monoclonal antibodies, antibody drug conjugates, immunomodulatory agents, intracellular pathway inhibitors, immune checkpoint inhibitors, and epigenetic regulators are discussed herein.
Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. [2023]Label="PURPOSE">Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes.
Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. [2023]Epcoritamab is a subcutaneously administered CD3xCD20 bispecific Ab that showed deep, durable responses with a manageable safety profile in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the global multicenter pivotal phase II trial EPCORE NHL-1. Here, we present results from the similar EPCORE NHL-3 phase I/II trial evaluating epcoritamab monotherapy in Japanese patients with R/R CD20+ B-cell non-Hodgkin's lymphoma previously treated with two or more lines of therapy. Epcoritamab was dosed subcutaneously in 28-day cycles; once weekly during cycles 1-3, every 2 weeks during cycles 4-9, and every 4 weeks from cycle 10 until disease progression or unacceptable toxicity. Step-up dosing and cytokine release syndrome (CRS) prophylaxis were used during treatment cycle 1. As of January 31, 2022, 36 patients received treatment with 48 mg epcoritamab monotherapy. At a median follow-up of 8.4 months, overall response and complete response rates by independent review committee were 55.6% and 44.4%, respectively. The median duration of response, duration of complete response, and overall survival were not reached at the time of data cut-off. The most common treatment-emergent adverse events of any grade were CRS (83.3%), injection-site reactions (69.4%), infections (44.4%), neutropenia (38.9%), hypokalemia (27.8%), and decreased lymphocyte count (25.0%). Cytokine release syndrome occurrence was predictable; events were primarily low grade (grade 1-2), all resolved, and none led to treatment discontinuation. These encouraging results are consistent with previous findings and support the ongoing clinical evaluation of epcoritamab for the treatment of R/R DLBCL, including in earlier treatment lines.