Epcoritamab Plus GemOX Exhibits Promising Early Efficacy in R/R DLCBL

Epcoritamab (DuoBody-CD3xCD20) in combination with gemcitabine plus oxaliplatin (GemOx) displayed encouraging responses with no new safety signals among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant (ASCT), according to initial results from the phase 1b/2 EPCORE NHL-2 trial (NCT04663347) presented during the 2022 European Hematology Association Congress.

At the March 25, 2022, data cutoff date, at a median follow-up of 9.2 months (range, 1-15), efficacy-evaluable patients (n = 25) achieved an overall response rate of 92%, including 60% of patients who experienced a complete molecular response (CMR) and 32% who had a partial molecular response. No patients had stable or progressive disease, and 2 patients did not undergo a response assessment.

Additional response profile data showed that the median duration of CMR was 7.5 months. At 6 months, approximately 76% of complete responders remained in CMR.

Arm 5 of the open-label, multicenter EPCORE NHL-2 trial is evaluating the safety and antitumor activity of the subcutaneously administered bispecific antibody epcoritamab plus GemOx in patients with relapsed/refractory DLBCL. To be eligible for the trial, patients needed to have CD20-positive disease and be ineligible for ASCT or have experienced prior ASCT failure. Other eligibility criteria included an ECOG performance status of 0-2, adequate organ function, and measurable disease by CT scan or MRI.

The combination was given over 4 cycles of 28 days, followed by epcoritamab monotherapy until disease progression. In the dose-escalation portion of the trial, patients were treated with epcoritamab 24 mg (n = 3) or 48 mg (n = 3) once weekly in cycles 1-3, twice weekly in cycles 4-9, and 4 times per week in cycle 10 and beyond. GemOX was administered twice weekly throughout cycles 1-4. The dose-expansion portion of arm 5 (n = 20) followed the same dosing schedule for the combination using 48 mg of epcoritamab.

The primary end points of the dose-escalation portion were dose-limiting toxicities and safety/tolerability. The key secondary end point of this part was antitumor activity. Additionally, the primary end point in the dose-expansion portion was antitumor activity.

Patients in arm 5 had a median age of 71 years (range, 47-87) and were divided evenly between males and females. Most patients had Ann Arbor stage IV disease (62%) and de novo DLBCL (73%). Twenty-seven percent of patients had an IPI score of 2 or less, 19% had a score of 3, and 38% had a score of 4 or 5.

The median time from diagnosis to first dose was 12 months (range, 1-76) and the median number of prior lines of therapy was 2 (range, 1-13). Notably 35% of patients received at least 3 prior lines of therapy, 38% of patients had 1 prior line of therapy, and 27% of patients underwent 2 prior lines of therapy. Prior ASCT and prior CAR T-cell therapy were administered to 12% of patients each.

Most patients had primary refractory disease (62%), and 73% of patients were refractory to their last line of therapy. Of the patients who were refractory to their last line of therapy, 46% relapsed within 6 months after treatment. Less than half of the patients in arm 5 were refractory to 2 or more consecutive lines of therapy (38%).

At the data cutoff date, 42% of patients were continuing treatment with epcoritamab plus GemOx. Patients discontinued treatment due to disease progression (23%), adverse effects (AEs; 19%), death (14%), and withdrawal by patient (4%).

In terms of safety, treatment with epcoritamab plus GemOx exhibited no new safety signals. Common grade 1 or 2 treatment-emergent adverse events (TEAEs) included cytokine release syndrome (CRS; 65%), hypomagnesemia (42%), nausea (38%), diarrhea (35%), and fatigue (35%). Grade 3 or 4 TEAEs included thrombocytopenia (61%), neutropenia (38%), and anemia (35%).

One patient experienced grade 3 immune effector cell-associated neurotoxicity syndrome and another had grade 3 febrile neutropenia. The any grade infection rate was 62% and the grade 3 or higher rate was 31%. No patients experienced clinical tumor lysis syndrome and 7 patients experienced grade 5 AEs.

Most cases of any grade CRS occurred following the first full dose (54%) with a median time to onset of 2 days (range, 1-5). Sixteen percent of patients experienced grade 1 or 2 CRS following the third full dose, 4% had grade 2 CRS after the second full dose, 4% had grade 1 CRS during the priming dose, and 8% had grade 1 or 2 CRS during the intermediate dose.

All patients who experienced any grade CRS eventually had the AE resolve. The median time to resolution was 2 days (range, 1-9) and no patients discontinued treatment with epcoritamab plus GemOx due to CRS. Tocilizumab was used to treat CRS in 5 patients. Investigators noted that CRS occurrence was predictable.

Study authors concluded that these positive initial findings warrant further clinical evaluation of epcoritamab plus GemOx in patients with relapsed/refractory DLBCL, given the high unmet treatment need in this population.

Reference

Wahlin BE, Brody J, Phillips T, et al. Subcutaneous epcoritamab with gemox induced high response rates in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplant. Poster presented at: 2022 European Hematology Association Congress; June 9-17, 2022; Vienna, Austria. Poster 1213.