Epcoritamab for Lymphoma
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Genmab
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). Classic Follicular Lymphoma is a slow-growing type of non-Hodgkin lymphoma. The purpose of this study is to assess the safety of epcoritamab in adult participants in relapsed or refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who have received at least 1 prior line of systemic antilymphoma therapy including at least 1 anti-CD20 monoclonal antibody-containing therapy or R/R classic follicular lymphoma (cFL). Adverse events will be assessed.
Epcoritamab is an investigational drug being developed for the treatment of R/R DLBCL and R/R cFL. Study doctors will assess participants in a monotherapy treatment arm of epcoritamab. Participants will receive escalating doses of epcoritamab, until full dose is achieved. Approximately 184 adult participants with R/R DLBCL and R/R cFL will be enrolled in the study in approximately 80 sites in the United States of America.
Participants will receive escalating doses of subcutaneous epcoritamab, until full dose is achieved, in 28-day cycles.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
What data supports the idea that Epcoritamab for Lymphoma is an effective treatment?The available research shows that Epcoritamab is effective for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In a study, 55.6% of patients showed an overall response, and 44.4% achieved a complete response, meaning their cancer was no longer detectable. These results are promising, especially for patients who have already tried other treatments without success. Additionally, Epcoritamab has shown strong anti-tumor activity in various types of B-cell non-Hodgkin lymphoma, even in patients who did not respond to previous treatments. This suggests that Epcoritamab could be a valuable option for those with limited alternatives.237910
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop your current medications. However, since the trial involves an investigational drug, it's possible that some medications might need to be adjusted. Please consult with the study doctors for specific guidance.
Is the drug Epcoritamab a promising treatment for Lymphoma?Yes, Epcoritamab is a promising drug for treating Lymphoma. It has shown strong anti-tumor activity, especially in patients with relapsed or hard-to-treat forms of the disease. It works by helping the body's immune cells target and destroy cancer cells. Epcoritamab has been approved for use in the USA and has received positive feedback in Europe, with ongoing studies worldwide.237910
What safety data is available for Epcoritamab in treating lymphoma?The provided research does not contain specific safety data for Epcoritamab or its other names (Epkinly, Tepkinly, epcoritamab-bysp). The studies focus on other treatments for lymphoma, such as Loncastuximab tesirine, Pembrolizumab with Vorinostat, CAR T-cell therapies, and immune checkpoint inhibitors. To find safety data for Epcoritamab, one would need to look for clinical trials or studies specifically evaluating Epcoritamab or its related names.14568
Eligibility Criteria
Adults with relapsed or refractory Diffuse Large B-Cell Lymphoma or Follicular Lymphoma, who have had at least two prior treatments including an anti-CD20 therapy. Participants must have adequate organ function and a performance status showing they can carry out daily activities with ease to moderate difficulty.Inclusion Criteria
My lymphoma is classified as 'double-hit' or 'triple-hit' DLBCL.
My condition has not improved after two cancer treatments, including one with anti-CD20.
My lymphoma shows up on scans and has at least one large tumor.
My lymphoma shows on scans with specific size tumors or nodes.
I am able to get out of my bed or chair and move around.
I have relapsed or refractory DLBCL or FL with CD20+ B-cells.
My lymphoma is classified as 'double-hit' or 'triple-hit' DLBCL.
Exclusion Criteria
My cancer has spread to my brain or spinal cord.
Treatment Details
The trial is testing Epcoritamab, an experimental drug for certain aggressive lymphomas. Patients will receive increasing doses of the drug through skin injections in cycles lasting 28 days each, to determine its safety and monitor any adverse effects.
4Treatment groups
Experimental Treatment
Group I: Main Cohort: Epcoritamab Diffuse Large B-Cell Lymphoma (DLBCL)Experimental Treatment1 Intervention
Participants with relapsed or refractory (R/R) DLBCL will receive subcutaneous (SC) epcoritamab in 28 day cycles.
Group II: Main Cohort: Epcoritamab Classic Follicular Lymphoma (cFL)Experimental Treatment1 Intervention
Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.
Group III: Diversity Enriched Cohort: Epcoritamab cFLExperimental Treatment1 Intervention
Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.
Group IV: Diversity Enriched Cohort: Epcoritamab DLBCLExperimental Treatment1 Intervention
Participants with R/R DLBCL will receive 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:
St. Joseph Mercy Hospital /ID# 244547Ypsilanti, MI
Clinical Research Philadelphia, LLCPhiladelphia, PA
Cancer Care Associates of York /ID# 254159York, PA
University of Rochester Cancer Center /ID# 245033Rochester, NY
More Trial Locations
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Who is running the clinical trial?
GenmabLead Sponsor
AbbVieIndustry Sponsor
References
Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database. [2020]Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers; however, they have been associated with immune-related adverse events (irAEs), among which cytokine release syndrome (CRS) has been reported in a few case reports. To describe the burden of ICI-related CRS and raise awareness of CRS as irAE, we queried VigiBase, the World Health Organization global database of spontaneously reported suspected adverse drug reactions (ADRs), and retrieved safety reports of suspected CRS associated with ICIs, gathered in the database through January 12th 2020. We assessed ICI-related CRS safety reports in terms of geographical and temporal patterns of reporting, patient demographics and clinical features, treatment characteristics, CRS clinical presentation, timing, seriousness, and outcome. We retrieved 58 cases of whom 43 (74%) reported CRS with anti-programmed death-1/anti-programmed death-ligand 1 agents. Melanoma (n=17, 29%) and hematologic malignancies (n=16, 28%) were the most common underlying cancers. ICIs were the solely suspected drugs in 37 (64%) cases. Typical signs and symptoms of CRS were reported in 25 (43%) patients. ICI-related CRS developed a median of 4 weeks after ICI initiation (IQR 1-18 weeks, n=9, 16%). Besides two fatal cases, CRS recovered/was recovering at the time of reporting in 35 (60%) cases. We observed differences in the geographical pattern of ICI-related CRS reporting, with a high proportion of ICI-related CRS cases in Australia and North America (0.14 and 0.10% respectively). Due to ICI expanding indications, clinicians should be aware that ICIs could contribute to CRS onset in cancer patients as pharmacological triggers.
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.
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. [2022]Loncastuximab tesirine-lpyl (ADC Therapeutics) is an anti-CD19 antibody-drug conjugate which consists of anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Data from preclinical in vitro and animal studies demonstrated its selectivity and efficacy. The phase I LOTIS-1 study for relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) demonstrated efficacy and a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia, elevated liver enzymes, and fluid accumulation. Based on pharmacokinetics analysis in this study, a dose of 150 μg/kg every 3 weeks for cycles 1 and 2 followed by 75 μg/kg every 3 weeks until disease progression or intolerability was chosen for the phase II LOTIS-2 study. This study recruited relapsed, refractory diffuse large B-cell lymphoma and confirmed similar safety profile. Overall response rate was 48.6% (24.1% complete response), and overall survival was 9.9 months. Due to its safety and efficacy reported in the above trials, loncastuximab tesirine was recently approved by the US Food and Drug Administration for the treatment of relapsed, refractory diffuse large B-cell lymphoma. Several clinical trials are ongoing to assess its safety and efficacy in NHL in various clinical settings.
Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. [2022]Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.
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.
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.
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.
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.