Preliminary Analysis of Data Evaluating Investigational Epcoritamab (DuoBody® CD3xCD20) Combination Demonstrates 95% Overall Response Rate in Patients with Previously Untreated Follicular Lymphoma
- Preliminary analysis of data from the EPCORE™ NHL-2 study demonstrates patients with previously untreated follicular lymphoma (FL) who received epcoritamab in combination with rituximab-lenalidomide (R2) experienced a 95% overall response rate (ORR)
- Results from the optimization cohort of the EPCORE™ NHL- 1 study show that mitigation strategies led to a clinically significant reduction in rate of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed/refractory (R/R) FL treated with epcoritamab
Separately, new data from the cycle 1 optimization part (C1 OPT) of the EPCORE™ NHL-1 study (NCT03625037), evaluating epcoritamab in patients with relapsed/refractory (R/R) FL, showed that following additional mitigation strategies, cytokine release syndrome (CRS) (any grade) was reported in 49 percent of patients vs. 66 percent of patients (any grade) in the pivotal cohort. Additionally, there were no Grade 3 or higher CRS events and no reported immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS are adverse reactions, which can be serious and/or life threatening. Patients need to be monitored and carefully managed per current practice guidelines. These results (Abstract #7015) were selected to be a part of Best of ASCO® (
FL is the second most common form of non-Hodgkin’s lymphoma (NHL), accounting for 20-30 percent of all NHL cases.i About 15,000 people develop FL each year in the
“Follicular lymphoma is considered incurable and patients at all stages of disease need innovative treatment options. Our data at this year’s ASCO suggest that epcoritamab can potentially provide promising overall and complete responses for patients with follicular lymphoma, whether previously untreated or post-relapse. Importantly, we’ve also focused on reducing incidence of CRS and ICANS through optimizing dosing safety of epcoritamab for patients with relapsed/refractory disease,” said
EPCORE™ NHL-2 Results in First-Line FL (Abstract #7014)
The EPCORE NHL-2 study analysis included results from two arms of the study. Arm 6 evaluated epcoritamab in combination with R2 in patients with previously untreated FL (n=41). With a median follow-up of 21.1 months, additional findings from this arm showed durable responses, with an estimated 89 percent of patients remaining progression free and 93 percent of patients who had achieved a CR remaining in CR at 18 months.
“The results from this preliminary analysis of epcoritamab in combination with rituximab-lenalidomide as a first-line, chemotherapy-free treatment for patients with FL are encouraging and support the continued evaluation of epcoritamab in this patient population,” said
The most common treatment-emergent adverse events (TEAEs) in these first-line patients were COVID-19 (63 percent), CRS (56 percent) and neutropenia (56 percent). All CRS events were low grade (41 percent Grade 1 and 15 percent Grade 2) and resolved. Most CRS events occurred after patients received their first full dose of epcoritamab, and none led to treatment discontinuation. Two fatal TEAEs occurred due to COVID-19 pneumonia and septic shock.
The EPCORE NHL-2 study results also included the first data disclosure from arm 7, which evaluated epcoritamab administered every 8 weeks for patients with first- or second-line FL in CR or partial response (PR) following standard-of-care treatment (n=20). Median follow-up was 19.7 months. An estimated 90 percent of patients remained alive at 21 months. Notably, 100 percent of patients who entered the arm with a PR converted to a CR (n=8).
In arm 7, the most common TEAEs were COVID-19 (70 percent) and CRS (55 percent). Only one CRS event (Grade 1) occurred during Q8W maintenance dosing. All other CRS events were during cycle 1 (C1) step-up dosing, as expected for these patients who had not previously received epcoritamab. One fatal TEAE occurred related to respiratory failure caused by post-acute COVID syndrome.
EPCORE™ NHL-1 Data in Later-line FL (Abstract #7015)
In this C1 optimization cohort in patients with R/R FL, patients received epcoritamab in 3 step-up doses (0.16, 0.8, and 3 mg), along with dexamethasone prophylaxis and hydration recommendations followed by full 48-mg doses until disease progression or unacceptable toxicity. There was no mandatory hospitalization. With a median follow-up of 5.7 months, CRS rate was 49% (Grade 1 40%, Grade 2 9%), primarily occurring during cycle 1, and all events resolved. CRS was adequately identified in the outpatient setting and appropriately treated. There were no ICANS events.
These findings show that mitigation measures implemented early in the epcoritamab treatment cycle may lead to substantial improvements in the incidence and severity of CRS and ICANS. Further, among the 81 response-evaluable patients in the cohort, ORR was 91 percent and CR rate was 68 percent, suggesting that the additional CRS mitigation did not impact efficacy.
On
About the EPCORE™ NHL-2 Trial
EPCORE™ NHL-2 isa phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, and preliminary efficacy of epcoritamab in combination with standard of care agents in patients with B-cell non-Hodgkin’s lymphoma, including FL, and across multiple lines of therapy. The trial consists of two parts – Part 1 (dose escalation) and Part 2 (dose expansion) – and 10 different treatment arms. The primary objective of Part 1 is safety, and it includes arm 1-5 and arm 10. Part 2 includes all 10 arms (arm 1-10) with the objective of preliminary efficacy. However, the primary objective of arm 7 is safety. More information on this trial be found at https://www.clinicaltrials.gov/ (NCT: 04663347).
About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 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 FL. 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 and generated pivotal data for patients with FL and diffuse large B-cell lymphoma (DLBCL). The optimization part evaluated additional cytokine release syndrome (CRS) mitigation strategies during cycle 1. The primary endpoint of the expansion part was ORR as assessed by an 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 first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.
About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.vi FL is the second most common form of NHL overall, accounting for 20-30 percent of all NHL cases, and represents 10-20 percent of all lymphomas in the western world.i,vii Although FL is an indolent lymphoma, it is considered incurable with conventional therapyand patients who achieve remission also often experience relapse.iii,iv,viii Additionally, with each relapse the remission and time to next treatment is shorterix, adding increased cost to the health system and negatively impacting the patient's quality of life.x
About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using
Epcoritamab (approved under the brand name EPKINLY in the
EPKINLY® (epcoritamab-bysp)
Important Warnings—EPKINLY can cause serious side effects, including:
- Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you may receive other medicines before receiving EPKINLY and you will also be given smaller doses of EPKINLY for the first 2 doses (called “step-up” dosing). Your first full dose of EPKINLY will be given on day 15 of your first cycle of treatment and you should be hospitalized for 24 hours after due to risk of CRS and neurologic problems. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
- Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. Do not drive or use heavy machinery or do other dangerous activities if you have any symptoms that impair consciousness until your symptoms go away.
EPKINLY can cause other serious side effects, including:
- Infections that may lead to death. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
- Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.
Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.
You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to
Please see Medication Guide, including Important Warnings.
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i
ii
iii Link BK, et al. Second-Line and Subsequent Therapy and Outcomes for Follicular Lymphoma in
iv Ren J, et al. Economic Burden and Treatment Patterns for Patients With Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the
v Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421.
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vii Luminari S, Bellei M, Biasoli I, Federico M. Follicular lymphoma—treatment and prognostic factors. Rev Bras Hematol Hemoter. 2012;34:54-59. doi: 10.5581/1516-8484.20120015.
viii
ix Rivas‐Delgado, A., Magnano, L., Moreno‐Velázquez, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br
x Kuruvilla J, Ewara EM,
xi Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625.
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