Epcoritamab Receives Positive CHMP Opinion for Relapsed/Refractory Follicular Lymphoma

The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use has announced a positive opinion in support of a conditional marketing authorization for epcoritamab (Tepkinly) for use as monotherapy in the treatment of patients with relapsed/refractory follicular lymphoma (FL) after 2 or more prior lines of systemic therapy.¹

The opinion, which will now be reviewed by the European Commission, is based on response data from the phase 1/2 EPCORE-NHL-1 trial (Study GCT3013-01; NCT03625037) showing an overall response rate (ORR) of 82.0% (95% CI, 74.1%-88.2%) and a complete response (CR) rate of 60.0% (95% CI, 50.8%-68.4%) with the IgG1 CD3- and CD20-directed bispecific antibody.^2,3

If approved, epcoritamab would become the first and only bispecific antibody to have conditional approval as a single agent in the European Union (EU) for the treatment of patients with relapsed/refractory FL and relapsed/refractory diffuse large B-cell lymphoma following at least 2 prior lines of systemic therapy.¹

“Many people living with FL that has either relapsed or is refractory to existing therapies experience significant treatment challenges with poor prognosis,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a news release.¹ “This positive opinion recognizes the unmet need in the EU for patients whose FL is considered difficult to treat and that epcoritamab may represent a new therapeutic option.”

The recommendation from the EMA comes just 2 days after the FDA approved epcoritamab in this same population.²

EPCORE-NHL-1 was designed as an open-label, multicenter trial to evaluate the efficacy and safety of subcutaneous epcoritamab through dose-escalation, -expansion, and -optimization phases in patients with relapsed/refractory non-Hodgkin lymphoma, including FL.¹

To be eligible for enrollment in the FL cohort, patients needed to have CD20-positive disease that was between grades 1 and 3A with prior receipt of at least 2 therapies, including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide (Revlimid). Patients were treated with 48 mg of epcoritamab, starting weekly for 3 cycles before transitioning to biweekly administration in cycles 4 through 9, and then every 4 weeks thereafter until disease progression or unacceptable toxicity.³ The first full dose of epcoritamab was administered on day 15 to allow patients to receive a 0.16-mg priming dose on day 1 and a 0.80-mg intermediate dose on day 8.

Notably the study population included patients who were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent, refractory to their last prior therapy, and those whose disease had progressed within 2 years of receiving first systemic therapy.¹

The primary end point of the expansion phase was ORR as assessed by independent review committee. Secondary end points included duration of response (DOR), CR, duration of CR, progression-free survival, and time to response according to Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary end points.

The rate of grade 2 or greater and all-grade cytokine release syndrome (CRS) events that occurred from the first dose of study therapy through 7 days after the second full dose of therapy served as the focus of the optimization phase.

Additional findings from the trial revealed that the median DOR was not reached (NR; 95% CI, 13.7-NR) at an estimated median follow-up of 14.8 months in responders.2 Responses occurred early and were durable with a median time to first response of 1.4 months (range, 1-3) and a Kaplan Meier–estimated 12-month DOR rate of 68.4% (95% CI, 57.6%-77.0%).³

Regarding safety, the most common adverse effects that occurred in at least 10% of patients were CRS, injection site reactions, pyrexia, neutropenia, anemia, thrombocytopenia, diarrhea, nausea, headache, upper respiratory tract infection, pneumonia, and rash.¹

Results from the optimization cohort were presented at the 2024 ASCO Annual Meeting. Among patients who received an optimized step-up dosing schedule of epcoritamab (n = 86), which included a second intermediate dose of 3 mg on day 15 in addition to 15 mg of prophylactic dexamethasone and hydration recommendations in the first cycle of treatment, 49% (n = 42) experienced CRS; 9% of these events were grade 2. No patients experienced grade 3 or higher CRS events in this cohort. Findings from this cohort compared favorably with those from the pivotal cohort (n = 128), in which the rate of any-grade CRS was 66% (n = 85), with grade 1, 2, and 3 events occurring in 40% (n = 51), 25% (n = 32), and 2% (n = 2) of patients, respectively. Immune effector cell–associated neurotoxicity syndrome also occurred in 6% (n = 8) of patients in this cohort.⁴

“Each year, thousands of people in Europe are diagnosed with FL, and it’s an upsetting reality that many of them will experience relapse and refractory disease,” Catherine Thieblemont, MD, PhD, head of the hemato-oncology department at Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris, in France, said in the news release.¹ “Patients deserve new treatment options, and this positive opinion is the first step to bringing epcoritamab to more patients who need it.”

References

1. Epcoritamab (TEPKINLY) receives positive CHMP opinion for the treatment of adults with relapsed/refractory follicular lymphoma. News release. Genmab A/S. June 28, 2024. Accessed June 28, 2024. https://www.globenewswire.com/news-release/2024/06/28/2905653/0/en/Epcoritamab-TEPKINLY-Receives-Positive-CHMP-Opinion-for-the-Treatment-of-Adults-with-Relapsed-Refractory-Follicular-Lymphoma.html
2. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. FDA. June 26, 2024. Accessed June 28, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma
3. Epkinly. Prescribing information. Genmab US, Inc; 2024. Accessed June 28, 2024. https://www.genmab-pi.com/prescribing-information/epkinly-pi.pdf
4. Vose J, Vitolo U, Lugtenburg P, et al. EPCORE-NHL-1 follicular lymphoma (FL) cycle (C) 1 optimization (OPT) cohort: expanding the clinical utility of epcoritamab in relapsed or refractory (R/R) FL. J Clin Oncol. 2024;42(suppl 16):7015. doi:10.1200/JCO.2024.42.16_suppl.7015