First-line odronextamab (Odro) plus chemotherapy (CHOP) in diffuse large B-cell lymphoma (DLBCL): OLYMPIA-3 Part 1B results.

Abstract

7009 Background: Approximately 25% of patients (pts) treated with rituximab + CHOP do not have a complete response (CR), and those with refractory/relapsed disease or high-risk features have poor outcomes. To address this unmet need, bispecific antibody combinations are being evaluated. In Part 1A (dose escalation) of the Phase 3 OLYMPIA-3 study (NCT06091865), odronextamab (Odro)-CHOP demonstrated generally manageable safety (most common treatment-emergent adverse events [TEAE] were neutropenia [81.8%] and cytokine release syndrome [CRS; 54.5%]) and encouraging preliminary efficacy in pts with previously untreated DLBCL, with CR rates of 100% on PET/CT (160 mg dose level, selected for Part 1B dose optimization). Here, we report Part 1B results. Methods: Part 1B included pts aged ≥18 years with untreated CD20+ DLBCL not otherwise specified or high-grade B-cell lymphoma with at least 1 high-risk feature. Odro-CHOP was administered in 6 × 21-day cycles, with Odro 0.7/4/20 mg step-up dosing from Cycle 1 Day 8. Pts were randomized 1:1 to receive Odro 160 mg QW/320 mg Q2W (Regimen [R] 1) or Odro 160 mg QW/160 mg Q3W (R2) with CHOP. Primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR) and CR rate per 2014 Lugano criteria. Results: At data cut-off (August 19, 2025), 40 pts were enrolled in Part 1B (20 per regimen). Median age was 67.5 years, 60.0% of pts were male, and 75.0% had an IPI score of 3–5. Median duration of treatment exposure was 18.1 weeks (R1) and 16.6 weeks (R2); 67.5% of pts completed 6 treatment cycles. Median relative dose intensity ranged from 90.1 to 100% for Odro and 92.7 to 100% for CHOP. The safety profile of Odro-CHOP was similar across regimens. TEAEs led to dose interruption/delay in 70.0% vs 50.0% of pts and to CHOP dose reduction in 10.0% vs 5.0% of pts with R1 vs R2, respectively. No TEAEs led to Odro dose reduction and 1 led to treatment discontinuation (Grade 4 neutropenic sepsis, R2). The most common TEAEs were neutropenia (57.5%), CRS (55.0%), and anemia (42.5%). CRS rates were consistent with Part 1A, predominantly Grade 1 (42.5% of pts). ICANS occurred in 3 pts (all Grade 1) and resolved completely. All enrolled pts were analyzed including 3 pts who discontinued treatment prior to tumor imaging assessment. With a median follow-up of 2.3 months in both regimens, ORRs were 95.0% (R1) and 90.0% (R2), and CR rates were 85.0% (both regimens). Conclusions: In Part 1B of OLYMPIA-3, the safety profile of Odro-CHOP was generally manageable and preliminary efficacy was encouraging with no meaningful differences between regimens, and combination with Odro did not impact the delivery of CHOP. Given these results, the less frequent Odro dosing regimen (R2) with CHOP was selected as the recommended Phase 3 dose for Part 2 (randomized controlled trial). Biomarker data will be presented. Clinical trial information: NCT06091865 .