Epcoritamab Yields Durable Responses in Relapsed/Refractory LBCL

An expansion cohort from the phase 2 EPCORE NHL-1 trial demonstrated strong efficacy of epcoritamab in patients with relapsed/refractory large B-cell lymphoma.

Epcoritamab (DuoBody- CD3xCD20) showed durable responses and efficacy for patients with relapsed/refractory large B-cell lymphoma (LBCL), according to results of the phase 2 EPCORE NHL-1 expansion cohort (NCT03625037) presented at the 2022 European Hematology Association Congress.1,2

An overall response rate (ORR) of 63% (95% CI, 55%-71%) with a complete response (CR) of 39% (95% CI, 31%-47%) was observed in the overall population of patients treated with epcoritamab (n = 157). In those who were naïve to CAR T-cell therapy, 69% had an ORR and 42% had a CR. Of the patients who had previously received CAR T-cell therapy, with an ORR of 54% and 34% had a CR. The median follow-up was 10.7 months and the median duration of response (DOR) was estimated to be 12 months. The median DOR for those achieving a CR was not reached, and 89% of patients were still in CR at 9 months.

“Large B-cell lymphoma is a fast-growing, difficult-to-treat type of aggressive non-Hodgkin’s lymphoma. Some treatment approaches like chemotherapy and immunotherapy have been in place for decades and newer treatments like CAR T-cell therapies involve multiple steps before a patient can begin treatment, so there is still a need for additional treatment options,” Catherine Thieblemont, professor and head of the Hemato-Oncology Department at Hôpital Saint-Louis in Paris, France, said in a news release. “The data presented today suggest that epcoritamab has the potential to provide patients living with LBCL an accessible, effective treatment with a safety profile that may fulfill an unmet need.”

Previous results were announced in April 2022 for patients who had received at least 2 prior lines of systemic therapy, 38.9% of whom had prior CAR T-cell therapy.3 The median number of lines of prior therapy was 3.5. Patients received weekly subcutaneous epcoritamab at 48 mg during cycles 1 to 3, biweekly doses during cycles 4 to 9, and 4 times per week for cycles 10 and beyond. Patients continued treatment until disease progression or unacceptable toxicity, with inpatient monitoring required for the first 24 hours.

Sixty-one percent of patients were refractory to prior treatment, 20% had prior autologous stem cell transplantation, and 39% had received CAR T-cell therapy. The median patient age was 64 years, with 50% having an ECOG performance score of 1. Of the entire cohort, 89% had diffuse large B-cell lymphoma, 70% had de novo diffuse large B-cell lymphoma (DLBCL), 9 patients had high-grade B-cell lymphoma, 4 had primary mediastinal LBCL, and 5 had follicular lymphoma of grade 3B.

Roughly 1 in 4 patients (24%) experienced progressive disease and 3% had stable disease with epcoritamab treatment. At data cutoff, 32% of patients were continuing treatment and 68% had discontinued due to progressive disease (53%), adverse effects (AEs; 7%), allogeneic stem cell transplant(4%), withdrawal by patients (3%), or other reasons (1%).

Consistent data were derived across subgroups, without regard for age, histology, CAR T-cell therapy exposure, and number of lines of prior treatment patients, for an ORR of 46%. In 96 patients who were naïve to CAR T-cell therapy, the ORR was 69% with 27% having a CR. Those who were older than 75 years (n = 29) had an ORR of 72% and those with transformed DLBCL (n = 40) had an ORR of 68%.

The median overall survival was not reached, and the rate at 6 and 12 months were 70.6% (95% CI, 62.7%-77.2%) and 56.9% (95% CI, 47.3%-65.4%), respectively. The median progression-free survival (PFS) was not reached in patients with CR, with 89% of those maintaining their response at 9 months. The median PFS in the overall population was 4.4 months (95% CI, 3.0-7.9) and the rate at 6 months was 43.9% (95% CI, 35.7%-51.7%).

AEs were mostly observed during the first 3 treatment cycles, with cytokine release syndrome (CRS; 49.6%), neutropenia (28%), pyrexia (23.5%), and fatigue (22.9%) occurring most frequently. Immune effector cell–associated neurotoxicity syndrome (ICANS) of grade 1 or 2 was observed in 9 patients, all of which resolved; 1 patient experienced a grade 5 ICANS. Of those who experienced CRS, 2.5% experienced grade 3 events. The median time to onset from the first full dose was 20 hours, with 98.7% of patients having full resolution of CRS. The median time to resolution from the first full dose was 48 hours. One patient discontinued treatment due to CRS.

References

  1. Thieblemont C, Phillips T, Ghesquieres H, et al. Primary results of subcutaneous epcoritamab dose expansion in patients with relapsed or refractory large B-cell lymphoma: a phase 2 study. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract LB2364
  2. AbbVie announced late-breaking results from phase 2 trial of investigational epcoritamab (DuoBody-CD3xCD20) in patients with relapsed/refractory large B-cell lymphoma (LBCL) at the European Hematology Association (EHA) Annual Congress. News Release. AbbVie. June 11, 2022. Accessed June 13, 2022. https://bit.ly/3zAcjf4
  3. AbbVie and Genmab announce topline results for Epcoritamab (DuoBody-CD3xCD20) from phase 1/2 trial in patients with relapsed/refractory large B-cell lymphoma (LBCL). News Release. AbbVie. April 13, 2022. Accessed June 13, 2022. https://bit.ly/3xJ16aC