Odronextamab, an IgG4-based CD20/CD3 bispecific antibody, demonstrated clinically meaningful efficacy, durable response, and manageable safety for patients with highly aggressive relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to results of a phase 2 trial.

Odronextamab has previously shown encouraging activity in patients with DLBCL who had previously received ≥2 lines of therapy in the ELM-1 study. The current results are from a prespecified analysis of the cohort receiving 160 mg, the recommended phase 2 dosing, odronextamab in the ELM-2 study.

These results were presented by Won-Seog Kim, MD, PhD, Samsung Medical Center, Seoul, South Korea, on December 11, at the 2022 American Society for Hematology Annual Meeting.

This analysis of the global, multicenter, phase 2 ELM-2 study included patients with DLBCL who had relapsed or were refractory to ≥2 lines of therapy, including an anti-CD20 antibody and an alkylator. The trial used an optimized step-up regimen where odronextamab was delivered intravenously in 21-day cycles with steroid prophylaxis and weekly step-up dosing during the first cycle. 

Patients received 1 mg split of day 1 and day 2 of the first cycle followed by 20 mg split over day 8 and day 9. The full 160 mg dose was administered on day 15 of cycle 1. This 1/20 regimen was modified during the trial to address cytokine release syndrome (CRS) risk. The modified regimen began with 0.7 mg split over day 1 and day 2 of the first cycle, 4 mg split over day 8 and day 9, 20 mg split over day 15 and day 16, followed by the full 160 mg dose administered on day 1 of cycle 2. For both regimens, the full dose was then administered until the end of cycle 4 and was followed by maintenance therapy of 320 mg odronextamab every 2 weeks. 

Treatment continued until disease progression or unacceptable toxicity. The primary end point was objective response rate.

At the data cut-off date of April 20, 2022, median duration of follow-up was 17.1 months. Data included 121 patients evaluated for safety and 90 evaluated for efficacy. The objective response rate was 53%, with a complete response rate of 37%. These results were seen across high-risk subgroups and a subgroup that received the modified regimen. The median duration of complete response was not reached (95% confidence interval [CI], 10.2 to not estimable). The probability of an ongoing complete response at 9 months was 73%.

Treatment-related adverse events occurred in 84% of patients. The most common events, occurring in >30% of patients, were cytokine release syndrome (53%), pyrexia (41%), and anemia (34%). After the implementation of the modified regimen, there were no grade ≥3 CRS events and all CRS events were resolved with supportive treatment. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 6% of patients on the 1/20 regimen, and in 4% of patients on the modified regimen. There were 7% of patients who discontinued treatment due to treatment-related adverse events. Two patients experienced a grade 5 adverse event.

Dr Kim and colleagues concluded, “The results of this study confirm the preliminary odronextamab activity observed in ELM-1, and collectively show odronextamab efficacy both before and after CAR T therapy in hard-to-treat, highly aggressive [relapsed/refractory] DLBCL, while at the same time demonstrating a manageable safety profile.” They added the modified odronextamab regimen “mitigates the risk of high-grade CRS, which has been observed consistently with other bispecifics and CAR T therapies and may present an important future option for the management of pts with [relapsed/refractory] DLBCL.”

Source:

Kim WS, Kim TM, Cho SG, 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. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 444.