Dr Matasar Discusses Successes of the Phase 3 OLYMPIA-3 Trial

Matthew Matasar, MD, Rutgers Cancer Institute, discusses the first results from a small, dose-escalation cohort (part 1) of the phase 3 OLYMPIA-3 trial (NCT06091865). The study suggests that the CD20 and CD3 bispecific antibody odronextamab (Ordspono) combined with standard CHOP chemotherapy demonstrates compelling early efficacy for patients with previously untreated diffuse large B-cell lymphoma (DLBCL). These initial data, presented at the 2025 ASH Annual Meeting, indicate that the combination yields deep and durable responses without requiring rituximab (Ritubxan).

In the dose-escalation cohort, odronextamab showed a dose-dependent improvement in response rates. Patients treated with the weekly 80 mg dose of odronextamab plus CHOP achieved an objective response rate (ORR) of 78% and a complete response (CR) rate of 44%. The weekly 160 mg dose group, however, demonstrated a superior 100% ORR and a 100% CR rate. The median duration of response and progression-free survival were not yet reached at the time of this early analysis. Based on the combination of efficacy and a manageable safety profile, the 160 mg dose was selected for Part 2 of the study, which will be a randomized comparison of odronextamab-CHOP (odro-CHOP) vs rituximab-CHOP (R-CHOP).

Regarding safety, the profile was generally manageable with no new safety signals. The most common grade 3 or higher treatment-emergent adverse event was neutropenia (81.8%). cytokine release syndrome (CRS) occurred in 54.5% of patients but was exclusively grade 1 or 2 in severity, primarily occurring during the initial step-up dosing phase. Infections were also common (81.8%), with 50% of patients experiencing opportunistic infections, such as CMV or COVID-19. Importantly, most patients were able to complete all six cycles of odronextamab-CHOP, with few dose reductions and no permanent discontinuations specifically due to odronextamab-related toxicities. These data support odronextamab as a promising novel agent in the first-line treatment of DLBCL.

REFERENCE

Michot J-M, Yagci M, Kargus K, et al. Odronextamab plus chemotherapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): First Results from part 1 of the Phase 3 Olympia-3 study. Blood. 2025;146 (Supplement 1):abstract 65. doi:10.1182/blood-2025-65