Epcoritamab for B-Cell Lymphoma
Recruiting in Palo Alto (17 mi)
+66 other locations
Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Genmab
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests a new drug, epcoritamab, for children and young adults with aggressive B-cell cancers that have come back or not responded to other treatments. The drug is given as an injection under the skin periodically. The study will check how safe the drug is and how well it works over several years.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but you cannot be receiving any anti-cancer therapy, including chemotherapy, radiotherapy, or other investigational agents, while participating.
What data supports the effectiveness of the drug Epcoritamab for B-cell lymphoma?
Epcoritamab has shown strong anti-tumor activity in patients with different types of B-cell lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, even in those who did not respond to previous treatments. In a study, 55.6% of patients with relapsed or refractory diffuse large B-cell lymphoma responded to the drug, with 44.4% achieving a complete response.
12345What is known about the safety of Epcoritamab for B-cell lymphoma?
Epcoritamab has shown a manageable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure), injection-site reactions, infections, and low white blood cell counts, but these were mostly mild and resolved without stopping treatment.
12456How is the drug Epcoritamab unique for treating B-cell 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 is particularly promising for patients with relapsed or refractory B-cell lymphoma who have not responded to other treatments.
12345Eligibility Criteria
This trial is for children and young adults (up to age 25) with aggressive B-cell lymphomas that haven't responded well to previous treatments. They should be able to perform daily activities at a certain level, have no other cancers needing treatment, and not currently be on anti-cancer therapies.Inclusion Criteria
I can do most activities but may need help.
My cancer has returned or didn't respond to initial treatment.
Exclusion Criteria
I am currently undergoing treatment for cancer.
My lymphoma has spread to my brain or spinal cord, confirmed by scans.
I am receiving treatment for another cancer.
Participant Groups
The study tests Epcoritamab's safety and effects in patients with relapsed/refractory mature B-cell neoplasms. Participants will receive the drug through subcutaneous injections over cycles of 28 days and will be monitored for at least three years.
1Treatment groups
Experimental Treatment
Group I: EpcoritamabExperimental Treatment1 Intervention
Participants will receive subcutaneous (SC) epcoritamab in 28 day cycles.
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:
Children's Hospital of Richmond at VCU /ID# 242770Richmond, VA
University of Texas Southwestern Medical Center /ID# 240892Dallas, TX
CHU Sainte-Justine /ID# 240766Montreal, Canada
Lucile Packard Children's Hospital /ID# 240854Palo Alto, CA
More Trial Locations
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Who is running the clinical trial?
GenmabLead Sponsor
AbbVieIndustry Sponsor
References
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.
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 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.
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.
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.
Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors (HDACi) exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in pre-clinical models. We therefore developed a phase I study to evaluate the safety and preliminary efficacy of Pembrolizumab with Vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase 2 dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma (NHL)). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered on twice daily on days 1-5 and 8-12 (dose-level (DL)1: 100mg; DL2: 200mg) and Pembrolizumab (200mg) was administered on day 1 of each 3-week cycle. Of 6 patients treated at DL1, 1 had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome (SJS)), and 1 of 6 had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, 9 had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11%/22% for FL and 45%/55% for all DLBCL. Amongst DLBCLs, the CR and ORR was 80%/80% for PMBL and 17%/33% for non-PMBL. In conclusion, Pembrolizumab with Vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL.