Epcoritamab Triplet Shows Early Promise in Relapsed/Refractory Follicular Lymphoma

Epcoritamab plus rituximab and lenalidomide yielded a 100% response rate in patients with relapsed or refractory follicular lymphoma.

Data reported from an arm of the EPCORE NHL-2 trial (NCT04663347) in patients with relapsed or refractory follicular lymphoma demonstrated impressive antitumor activity of a combination involving subcutaneous epcoritamab (GEN3013; DuoBody-CD3xCD20) in combination with rituximab (Rituxan) and lenalidomide (Revlimid; R2), according to data presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1

Of the 28 evaluable patients in arm 2a, all achieved a response to treatment with the triplet regimen at any time point, and complete metabolic response was achieved in 96% of patients with the remaining patient achieving a partial metabolic response. Ninety-three percent of patients maintained a response at 6 weeks and the other 7% had stable disease.

“Epcoritamab with R2 showed encouraging results with all patients in arm 2a achieving a response, and most a complete response,” said Lorenzo Falchi, MD, a medical oncologist in the Lymphoma Service at Memorial Sloan Kettering Cancer Center, in a prerecorded presentation of the poster.

Epcoritamab is a bispecific antibody that binds to CD3 on T cells and CD20 on B cells and is administered subcutaneously.

Previously in a phase 1/2 clinical trial (NCT03625037), epcoritamab monotherapy at 48 mg induced an 88% overall response rate among 68 evaluable patients with heavily pretreated B-cell non-Hodgkin lymphoma and a complete response rate of 45%.2

In the ongoing open-label EPCORE NHL-2 study, investigators are exploring combination of epcoritamab and various other agents for treating patients with B-cell non-Hodgkin lymphoma.

Arm 2 of the trial focused on the triplet regimen of rituximab and lenalidomide with epcoritamab, administered at 2 different schedules in the 2 expansion cohorts. In the dose-escalation cohort patients received step-up dosing for epcoritamab at 24 mg (n = 3) or 48 mg (n = 3) weekly for the first 3 cycles, then every 2 weeks for the next 6 cycles, and every 4 weeks thereafter. Intravenous rituximab was administered weekly at 375 mg/m2 for cycle 1 and every 4 weeks for cycles 2 through 5, and oral lenalidomide was administered at 20 mg daily for 21 days of each of the 12 cycles. Corticosteroid prophylaxis was also given.

In the first expansion cohort, patients received subcutaneous epcoritamab 48 mg at the prior schedule (cohort 2a), and the second expansion arm (cohort 2b) received epcoritamab at 48 mg weekly for the first 2 cycles and then every 4 weeks thereafter, both with the standard doses for R2.

Eligible patients were those with relapsed/refractory CD20-positive follicular lymphoma of grade 1 to 3A and stage II to IV. All patients were required to have symptoms or disease burden by GELF criteria, an ECOG performance status of 0 to 2, measurable disease, and adequate organ function.

The primary end point of the dose-escalation cohort was dose-limiting toxicities and safety and tolerability and that of the expansion arms was antitumor activity.

Patients in arm 2b (n = 44) tended to have received more prior therapies and have a higher performance status than those in arm 2a (n = 30). The median age of patients in arm 2a was 68 years old (range, 42-80), 57% were female, 70% had Ann Arbor stage IV disease, 30% had primary refractory disease, and 27% were refractory to their most recent therapy. The median time from diagnosis to starting treatment with the triplet was 89 months (range, 6-281) and the median number of prior lines of therapy was 1 (range, 1-5) in cohort 2a.1

In cohort 2b, the median age was 66 (range, 30-79), 50% were female, 61% had Ann Arbor stage IV disease, 27% had primary refractory disease, and 27% were refractory to their most recent therapy. The median time from diagnosis to starting treatment with the triplet was 73 months (range, 4-331) and the median number of prior lines of therapy was 2 (range, 1-9) in cohort 2a.

Patients in arm 2a were followed for a median of 8.6 months (range, 3.3-14.6) with 77% still receiving treatment at the time of the data cutoff date of March 25, 2022. The median duration of treatment was 8.5 months (range, 0.3-13.3). In arm 2b, the median follow-up was 2.2 months (range, 0-4.7).

“Based on response rates at 6 weeks, patients in arm 2b also achieved encouraging efficacy,” Falchi explained.

Among 28 evaluable patients in the cohort, the overall response rate in arm 2b was 93%, with complete metabolic response achieved by 61% and partial metabolic response in 32%. Stable disease and progressive disease were reported in 1 patient each.

Treatment-emergent adverse events (TEAEs) led to epcoritamab dose delay in 43% of patients and discontinuation in 7% in arm 2a, however, no fatal TEAEs were reported in the cohort to date. The most common TEAEs in arm 2a of any grade were injection-site reactions in 53% of patients, cytokine release syndrome (CRS) in 50%, constipation in 47%, neutropenia in 47%, fatigue in 40%, cough in 37%, and rash in 33%. Neutropenia was the most frequent TEAE observed at grade 3 or 4.

CRS was grade 1 in 30% of patients, grade 2 in 13%, and grade 3 in 7%, but resolved in all patients at a median of 4 days (range, 1-15). CRS led to treatment discontinuation in only 1 patient and 3 patients required treatment with tocilizumab (Actemra). Occurrence of CRS was mostly predictable with most cases happening after the first full dose by cycle 1, day 15.

One case of immune effector cell–associated neurotoxicity was reported at a grade 2 in severity, but the event resolved in 4 days and did not lead to treatment discontinuation. TEAEs from cohort 2b were not reported as treatment is ongoing and follow-up is limited in the cohort, but thus far no new safety signals have been observed.

The poster authors noted that these updated data support further exploration of epcoritamab plus R2 in patients with relapsed/refractory follicular lymphoma.

References

  1. Falchi L, Leppä S, Wahlin BE, et al. Subcutaneous epcoritamab with rituximab + lenalidomide (R2) in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Update from phase 1/2 trial. J Clin Oncol. 2022;40(suppl 16):7524. doi:10.1200/JCO.2022.40.16_suppl.7524
  2. Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021;398(10306):1157-1169. doi:10.1016/S0140-6736(21)00889-8