First-Line Odronextamab Plus Chop in Diffuse Large B-Cell Lymphoma: Olympia-3 Part 1b Results
Recommended Citation
von Tresckow B, Matasar M, Jandl T, Assi R, Kuriakose P, Iragavarapu C, Illmer T, Goldschmidt N, Avigdor A, Jeon Y, Ong S, Yannakou CK, Sia H, Shin H, Wong Lee Lee L, González de Villambrosia Pellón S, Kori AN, De Vriendt C, von Keudell G, Amorim S, Musuraca G, Tani M, Martin ED, Garcia AG, Brouwer-Visser J, Kargus K, Mohamed H, Cao A, Iqbal N, Michot J. First-Line Odronextamab Plus Chop in Diffuse Large B-Cell Lymphoma: Olympia-3 Part 1b Results. J Clin Oncol 2026; 44(16_SUPPL):1.
Document Type
Conference Proceeding
Publication Date
5-27-2026
Publication Title
J Clin Oncol
Keywords
biological marker, bispecific antibody, cyclophosphamide, doxorubicin, odronextamab, rituximab, vincristine, adult, anemia, B cell lymphoma, clinical trial, conference abstract, controlled study, cytokine release syndrome, cytomegalovirus infection, diffuse large B cell lymphoma, drug dose reduction, drug dose regimen, drug therapy, female, follow up, human, male, multiple cycle treatment, neutropenia, positron emission tomography-computed tomography, randomized controlled trial, sepsis, side effect, treatment duration
Abstract
Background Approximately 25% of patients (pts) with diffuse large B-cell lymphoma (DLBCL) 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 [TEAEs] 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 positron emission tomography/computed tomography (160 mg dose level, selected for Part 1B dose optimization). Aims To evaluate the safety and efficacy of 2 dosing regimens of Odro-CHOP in Part 1B. Methods Part 1B included pts aged ≥18 years with untreated CD20+ DLBCL not otherwise specified with at least 1 high-risk feature or high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangement. Odro-CHOP was administered in 6 × 21-day cycles, with Odro 0.7/4/20 mg step-up dosing from Cycle (C) 1 Day (D) 8. Pts were randomized 1:1 to receive Odro 160 mg QW on C2D8–C5D1 then 320 mg Q2W on C5D8–C6D15 (Regimen [R] 1), or Odro 160 mg QW on C2D8 and C2D15 then 160 mg Q3W on C3D1–C6D1 (R2), plus CHOP. The primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), CR rate, and duration of response (DOR) per 2014 Lugano criteria. Exploratory endpoints included biomarker analysis. 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 was 90.1% in R1 and 100% in R2 for Odro, and 98 to 100% for cyclophosphamide, doxorubicin, and vincristine (CHO) in both regimens. The safety profile of Odro-CHOP was similar in both 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. TEAEs led to treatment discontinuation in 1 pt (Grade 4 neutropenic sepsis, R2). The most common TEAEs were neutropenia (57.5%), CRS (55.0%; predominantly Grade 1 [42.5% of pts]), and anemia (42.5%). ICANS occurred in 3 pts (all Grade 1) and resolved completely. As mandated by the protocol, cytomegalovirus (CMV) monitoring was performed via blood PCR. CMV infections (high-level term) occurred in 20 pts; 7 were symptomatic infections. Efficacy was analyzed as ITT, 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). Median DOR and duration of CR: not reached. Analyses of pts who reached end of treatment showed 8/12 pts in R1 and 7/13 pts in R2 had undetectable ctDNA (Figure). Summary/Conclusion In Part 1B of OLYMPIA-3, the safety profile ofOdro-CHOP was generally manageable, preliminary efficacy was encouraging with no meaningful differences between regimens, and combination with Odro did not impact the delivery of CHO. 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). (Figure presented)
Volume
44
Issue
16_SUPPL
First Page
1
