Saturday, July 13, 2024

Follicular Lymphoma Treatment Gets Boost with Positive CHMP Opinion for TEPKINLY®

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Genmab announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of conditional marketing authorization for epcoritamab (TEPKINLY®) for follicular lymphoma (FL). This T-cell-engaging bispecific antibody, administered subcutaneously, is recommended as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma after two or more lines of systemic therapy. The final decision from the European Commission on this indication for epcoritamab is anticipated later this year.

The positive CHMP opinion is based on the results from the Phase 1/2 EPCORE® NHL-1 study, which demonstrated durable and clinically meaningful treatment responses in patients with challenging-to-treat R/R follicular lymphoma. FL is the second most common type of non-Hodgkin’s lymphoma (NHL), accounting for approximately 20-30 percent of all global cases. If approved, epcoritamab (TEPKINLY®) would become the first and only bispecific antibody conditionally approved as a monotherapy in the European Union to treat both R/R follicular lymphoma and R/R diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

“Many people living with follicular lymphoma that has either relapsed or is refractory to existing therapies experience significant treatment challenges with poor prognosis,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “This positive opinion recognizes the unmet need in the European Union for patients whose follicular lymphoma is considered difficult to treat and that epcoritamab may represent a new therapeutic option.”

CHMP Opinion for Epcoritamab Supported by Strong Phase 1/2 Trial Data in Follicular Lymphoma

The CHMP opinion is supported by overall and complete response data from the Phase 1/2 EPCORE® NHL-1 clinical trial, which involved 128 patients with R/R follicular lymphoma treated with epcoritamab after two or more lines of systemic therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, as well as patients who were refractory to their last prior treatment or whose disease progressed within two years of their first systemic therapy.

The trial reported an overall response rate (ORR) of 82% and a complete response (CR) rate of 60%, with 67% of patients achieving minimal residual disease (MRD) negativity. More than half of the patients who responded to epcoritamab treatment remained responsive at the time of data analysis, with a median follow-up of 14.8 months and the median duration of response (DoR) not yet reached. These results were recently published in The Lancet Haematology.

In the trial, the most common (≥10%) adverse reactions included cytokine release syndrome (CRS), injection site reactions, pyrexia, neutropenia, anemia, thrombocytopenia, diarrhea, nausea, headache, upper respiratory tract infection, pneumonia, and rash. An additional cohort of 86 patients evaluated an optimized step-up dosing (SUD) schedule to reduce the incidence and severity of CRS, which is an associated side effect of immune-engaging cancer treatments. Hospitalization was not mandatory in the optimization cohort.

The incidence of CRS was 49% (42 of 86 patients; 9% were grade 2), and there were no grade 3 or higher CRS events in the optimization cohort. The EPCORE NHL-1 results, including those from the optimization cohort, were recently published in The Lancet Haematology. Additionally, data from the optimization cohort were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and selected to be part of Best of ASCO® (July 19-20, Boston, MA), as well as presented at the 2024 European Hematology Association (EHA) Congress.

Follicular Lymphoma

New Hope for Follicular Lymphoma Patients as Epcoritamab Shows Promising Trial Results

“Each year, thousands of people in Europe are diagnosed with follicular lymphoma, and it’s an upsetting reality that many of them will experience relapse and refractory disease,” said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department at Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. “Patients deserve new treatment options, and this positive opinion is the first step to bringing epcoritamab to more patients who need it.”

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The EPCORE® NHL-1 trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part, an expansion part, and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), including follicular lymphoma. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The expansion part generated pivotal data from patients with FL and DLBCL. The optimization part evaluated additional CRS mitigation strategies during cycle 1.

The primary endpoint of the expansion part was the overall response rate (ORR) as assessed by an Independent Review Committee (IRC). Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from the first dose of epcoritamab through seven days following administration of the second full dose of epcoritamab.

Epcoritamab Offers New Hope for Follicular Lymphoma Patients with Promising Trial Results

Follicular lymphoma is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes. Although FL is an indolent lymphoma, it is considered incurable with conventional therapy, and patients who achieve remission often experience relapse. Generally, with each relapse, the remission and time to the next treatment are shorter. Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody® technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells, inducing T-cell-mediated killing of CD20+ cells.

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R follicular lymphoma indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials, including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigator’s choice chemotherapy, a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL, a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL, and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated follicular lymphoma.

 

Resource: Genmab, June 28, 2024

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