Ayyappan Discusses the Phase 2 ELM-2 Trial of Odronextamab in DLBCL

Sabarish Ram Ayyappan, MD, medical director of hematologic malignancies, City of Hope Cancer Treatment Center, Atlanta, discusses the mechanism of action of odronextamab (REGN1979) and highlights the phase 2 ELM-2 trial (NCT03888105) which evaluated the agent in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The open-label, multicohort, multicenter, phase 2 study enrolled patients with relapsed/refractory DLBCL per WHO 2016 classification who had an ECOG performance status score of 0 or 1, and had disease that was refractory to or relapsed after 2 or more prior lines of therapy, including an anti-CD20 antibody and an alkylator.

Patients were treated with weekly odronextamab administered in 21-day cycles. In cycle 1, odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg. In cycle 2 through 4, patients received odronextamab at 160 mg on days 1, 8, and 15 of each cycle. Then, the maintenance therapy consisted of 320 mg odronextamab every 2 weeks. Treatment was continued until disease progression or unacceptable toxicity.

The primary end point of the study was overall response rate (ORR) by independent committee review. Secondary end points included ORR by local investigator, complete response, duration of response, progression-free survival, and overall survival. Investigators also evaluated safety, tolerability, and patient-reported outcomes, and minimal residual disease served as an exploratory end point of the study.

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0:10 | Patients with relapsed and refractory diffuse large B-cell lymphoma tend to have poor outcomes. There have been newer therapies that have been approved include CAR [chimeric antigen] T-cell therapy, but patients do relapse post CAR T, so there is a need for novel agents.

0:23 | The new class of drugs called bispecific antibodies have been exciting in this class for treatment of patients with relapsed and refractory diffuse large B-cell lymphoma. Odronextamab is a human IgG4 anti-CD3/CD20 bispecific antibody that has shown activity in diffuse large B-cell lymphoma and other non-Hodgkin lymphoma. As part of evaluating the efficacy and safety of this drug, the phase 2 study was designed and enrolled patients in a global cohort of diffuse large B-cell lymphoma patients who had relapsed and [were] refractory after 3 lines of therapy, including an anti-CD20 alkylator therapy.

1:03 | The study started enrollment in March 2020 and completed enrollment in May 2022, enrolling patients from 14 different countries globally. There are patients that had some high-risk characteristics, including double-hit lymphoma. Twenty percent of patients had transformed lymphoma as a characteristic, [and] patients of older age greater than 75 years of age are constituted about 24% of the patient as well.