Odronextamab, an investigational bi-specific antibody targeting CD20 and CD3, showed promising anti-tumor activity in heavily pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 study. The agent also had a manageable safety profile.

The phase 1 ELM-1 trial evaluated odronextamab in patients with relapsed/refractory DLBCL.1 The positive results of this trial instigated the pivotal phase 2 ELM-2 trial.2 Here, the study population was divided into five disease-specific cohorts. The DLBCL cohort included 140 patients who relapsed after or were refractory to at least two lines of therapy. After a 21-day step-up cycle, patients received 160 mg odronextamab once weekly, intravenously administered for three cycles. They then received 320 mg biweekly. The primary endpoint was objective response rate (ORR) by independent central review. Dr. Won-Seog Kim (Samsung Medical Center, South Korea) presented the first interim results at the 2022 annual meeting of the American Society of Hematology.

After a median follow-up of 21.3 months, the ORR was 49.2%, with a complete response (CR) rate of 30.8% and a partial response (PR) rate of 18.5%. Dr. Kim added that results from an expansion cohort of the phase 1 ELM-1 study (N=30) showed that the ORR was 48.4% (CR, 32.3%; PR, 16.1%) in patients who had received prior CAR T therapy. Furthermore, in the phase 2 study, the median duration of response was 10.2 months, and the median duration of CR was 17.9 months.

A grade 3 or higher treatment-emergent adverse event (AE) occurred in 52.9% of patients. The most common any grade, treatment-emergent AEs were cytokine release syndrome (CRS; 54.3%), pyrexia (22.1%), neutropenia (20.7%), and anemia (20.0%). Treatment-emergent AEs led to treatment discontinuation in 7.9% of participants. Dr. Kim added that the optimized step-up regimen reduced the incidence of grade 2 and 3 CRS events to 13.7% and 1.4%, respectively. Infections of grade 3 or higher were seen in 32.9% of participants. Immune effector cell-associated neurotoxicity syndrome (ICANS) was rare, with only 1 grade 3 event in all participants.

According to the authors, phase 3 trials will be initiated to investigate this agent in earlier lines of therapy.


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