Odronextamab has considerable anti-tumour effects in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

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

The phase 1 ELM-1 trial (NCT02290951) evaluated odronextamab in patients with relapsed/refractory DLBCL [1]. The positive results of this trial instigated the pivotal phase 2 ELM-2 trial (NCT03888105) [2]. Here, the study population was divided in 5 disease-specific cohorts. The DLBCL cohort included 140 patients who relapsed after or were refractory to at least 2 lines of therapy. After a 21-day step-up cycle, patients received 160 mg odronextamab once weekly, intravenously administered for 3 cycles. Hereafter, they received 320 mg biweekly. The primary endpoint was the objective response rate (ORR) by independent central review. Prof. Won-Seog Kim (Samsung Medical Center, South Korea) presented the first interim results.

After a median follow-up time 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%. Prof. 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 treatment-emergent adverse event (AE) occurred in 52.9% of the patients. The most common, any grade, treatment-emergent AEs were cytokine release syndrome (CRS; 54.3%), pyrexia (22.1%), neutropenia (20.7%), and anaemia (20.0%). Treatment-emergent AEs led to treatment discontinuation in 7.9% of the participants. Prof. Kim added that the optimised step-up regimen reduced the incidence of grade 2 and 3 CRS events to 13.7% and 1.4%, respectively. Infections of grade ≥3 were seen in 32.9% of the participants. Finally, immune effector cell-associated neurotoxicity syndrome (ICANS) was rare, with only 1 grade 3 event in all participants.

Prof. Tae Min Kim (Seoul National University Hospital, South Korea) presented the results of the cohort of patients with follicular lymphoma who were refractory to or relapsed after ≥2 lines of therapy (n=131) [3]. The ORR by independent central review in this patient population was 81.8% after 22.4 months of follow-up, with a CR rate of 75.2%. Prof. Kim added that the ORR after 12 weeks was comparable in patients who received the 1/20 mg step-up regimen (72.1%) and in patients who were exposed to the 0.4/7/20 mg step-up regimen (75.5%). The results were consistent across high-risk subgroups. Furthermore, the median duration of response was 20.5 months, and the median progression-free survival was 20.2 months. In this population of patients with relapsed/refractory follicular lymphoma, 77.9% of the patients experienced at least 1 grade 3 or higher treatment-emergent AE. The safety profile was comprised of a similar pattern of AEs as in the DLBCL group.

The first results of the phase 2 ELM-2 trial showed the encouraging efficacy and manageable safety profile of odronextamab in patients with either heavily pre-treated DLBCL or heavily pre-treated follicular lymphoma. Phase 3 trials will be initiated to further assess this agent in these disease areas.

1. Bannerji R, et al. Lancet Haematol. 2022;9(5):e327–e339.
2. Kim WS, et al. Odronextamab in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2. Abstract 444, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.
3. Kim T, et al. Odronextamab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1–3a: Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2. Abstract 949, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February, 2023