Investigators reported topline findings from the phase 1/2 EPCORE NHL-1 trial assessing epcoritamab in patients with relapsed/refractory large B-cell lymphoma.
Topline findings from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), which examined epcoritamab (DuoBody®-CD3xCD20) in patients with relapsed/refractory large B-cell lymphoma (LBCL) following 2 prior lines of therapy, read out in a press release from developer Genmab.1
Epcoritamab elicited an overall response rate (ORR) of 63.1% by independent review committee. The median duration of response was 12 months, and the most common treatment-emergent adverse effect (TRAEs) was cytokine release syndrome (CRS; 49.7%), of which 2.5% of cases were grade 3.
Additional results will be presented at an upcoming meeting.
“Together with our partner, AbbVie, we will work with regulatory authorities to determine next steps and continue to evaluate epcoritamab in a variety of clinical trials as a potential treatment option for patients with various hematological malignancies,” Jan van de Winkel, PhD, chief executive officer at Genmab, said in the press release.
The trial is made up of 2 parts, including dose escalation, and dose expansion. Results from the dose escalation portion were previously reported in The Lancet Oncology.2 Currently, the second part of the study has enrolled 3 cohorts of patients with relapsed/refractory B-cell non-Hodgkin lymphomas to explore the safety and efficacy of epcoritamab.
The dose escalation portion included 73 patients, of whom 68 received escalating full doses of epcoritamab at 24 mg or less (n = 53), 48 mg (n = 12), or 60 mg (n = 3). Among these patients, 68 had diffuse LBCL, 12 had follicular lymphoma, 6 had mantle cell lymphoma, and 3 had high-grade B-cell lymphoma. The remaining 3 patients had primary mediastinal LBCL, small lymphocytic lymphoma, and marginal zone lymphoma.
A total of 94% of patients had an ECOG performance status of 0 or 1 and all were refractory to or relapsed following treatment with an anti-CD20 monoclonal antibodies. Additionally, 99% had previous chemotherapy, 85% had a median of 3 previous lines of therapy and were refractory to the last line of therapy, and 9% had previous CAR T-cell therapy.
By the data cut off, 15 patients remained on treatment. The most common reason for discontinuation was progressive disease (68%). It was also noted that 1 patient had an unrelated fatal adverse effect, COVID-19 pneumonia.
Those who received 24 mg of epcoritamab had a median duration of exposure of 8.1 weeks, 48 mg was 11.8 weeks, and 60 mg was 40.1 weeks. Patients did not experience any dose-limiting toxicities or dose reductions during the dose-limiting toxicity evaluation period, and the maximum tolerated dose was not reached up to the highest dose of 60 mg.
The most common TRAEs were pyrexia (69%), CRS (59%), and injection site reaction (47%). Serious AEs were observed in 68% of patients, the most common of which were pyrexia
and pneumonia. Pyrexia was the only serious TRAE that occurred in 5% of patients.
AEs of special interest included CRS, neurological events, and clinical tumor lysis syndrome. Most CRS events occurred during cycle 1 and were manageable. The median time to the onset of CRS after the first dose was 1.4 days, and after the full dose it was 1.8 days. All patients who experienced CRS recovered.
During treatment, 11 patients died. A total of 38 patients died on the study with the most common reason being disease progression (n = 33). Other causes of death were lymphoma, graft-versus-host disease, and septic shock, which included 1 patient each.
Dosing from 0.76 mg to less than 12 mg yielded an ORR of 13% (95% CI, 2%-38%), complete response (CR) of 13% (95% CI, 2%-38%). With a dose ranging from 12 mg to 60 mg, the ORR of 68% (95% CI, 45%-86%), and a CR of 45% (95% CI, 24%-68%). Finally, a dose of 48 mg to 60 mg resulted in an ORR of 91% (95% CI, 59%-100%), and a CR of 55% (95% CI, 23%-83%).