Odronextamab Plus CHOP Demonstrates High Response Rates and Manageable Safety for Previously Untreated DLBCL: First Results From OLYMPIA-3 Trial
Key Clinical Summary
- Population and Design: Phase 3 OLYMPIA-3 trial (NCT06091865) evaluated odronextamab (CD20-CD3 bispecific antibody) plus CHOP chemotherapy in 22 untreated DLBCL patients (median age 66 y), testing 2 dose levels (DL1: 80 mg; DL2: 160 mg) over 6 cycles.
- Efficacy: ORR 77.8% (DL1) and 100% (DL2); CR 44% (DL1) and 100% (DL2); median DOR not reached; 6-month event-free probability 85.7% (DL1) and 90.0% (DL2), indicating deep, durable responses at higher dosing.
- Safety: No DLTs observed; grade ≥ 3 neutropenia common (DL1 77.8%, DL2 84.6%); CRS (33–77%) was low-grade, and grade ≥ 3 infections (22–62%) occurred. Results demonstrate manageable safety and encouraging early efficacy, supporting Odro-CHOP as a potential rituximab-free frontline regimen for DLBCL.
According to research presented by Jean-Marie Michot, MD, Gustave Roussy, Villejuif, France, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida, odronextamab (Odro), combined with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) chemotherapy achieves high response rates and manageable toxicity for previously untreated diffuse large B-cell lymphoma (DLBCL).
Researchers conducted the Phase 3 OLYMPIA-3 study (NCT06091865) to evaluate odronextamab, a CD20-CD3 bispecific antibody, with CHOP chemotherapy among patients with untreated DLBCL. The study consists of part 1A (dose escalation) and part 1B (dose optimization). These results are derived from part 1A.
In this portion of the trial, patients received step-up intravenous odronextamab dosing beginning in Cycle 1, followed by 6 total cycles of odronextamab plus CHOP. Two dose levels were tested including 80 mg (DL1, n=9) and 160 mg (DL2, n=13). The primary end points were incidence of dose-limiting toxicities (DLTs) during the DLT observation period and incidence of treatment-emergent adverse events. Secondary end points were objective response rate (ORR), complete response (CR) rate, and duration of response (DOR).
Overall, 22 patients were included, and the median age of patients was 66 years (range, 24 to 81). No DLTs were identified during the DLT observation period. Treatment-emergent adverse events occurred in all patients, with neutropenia being the most frequent grade ≥ 3 adverse event (DL1, 77.8%; DL2, 84.6%). Cytokine release syndrome (CRS) occurred in 33.3% of DL1 and 76.9% of DL2 patients, all low-grade (grade 1 or 2). Grade ≥ 3 infections were reported among 22.2% of patients in the DL1 group and 38.5% in the DL2 group.
The ORR for patients in the DL1 group was 77.8% (95% CI, 40.0 to 97.2) and 100% (95% CI, 75.3 to 100) for patients in the DL2 group. The CR rate was 44% (95% CI, 13.7 – 78.8) in the DL1 group and the CR rate was 100% (95% CI, 75.3 to 100) for patients in the DL2 group. The median DOR was not reached in either group and the 6-month event-free probability was 85.7% for patients in the DL1 and 90.0% in the DL2 group.
The researchers concluded, “in part 1A of the phase 3 OLYMPIA-3 study, the safety profile of Odro-CHOP induction was generally manageable, with no new safety signals.”
They added, “preliminary efficacy of this simplified regimen was encouraging, with a CR rate of 100% for DL2, suggesting that rituximab may not be required to achieve depth of response when combining Odro with CHOP in previously untreated [patients] with DLBCL.”
Source:
Michot JM, 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. Dec 6-9, 2025; Orlando, FL. Abstract: 65
