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ASH 2025 | Phase III Olympia-3 trial first results: O-CHOP vs R-CHOP in previously untreated DLBCL
Matthew Matasar, MD, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, presents early results from the Phase III OLYMPIA-3 study (NCT06091865) evaluating odronextamab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (O-CHOP) versus rituximab-CHOP (R-CHOP) for previously untreated diffuse large B-cell lymphoma (DLBCL). He discusses dose optimization findings, supporting full-dose odronextamab as the regimen moves toward randomized evaluation. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So, we recognize as a field the emerging importance of bispecific antibodies and improving clinical outcomes, and we’ve seen monotherapy in the multiple-relapse setting. We’ve seen combination approaches in the second line and beyond. Certainly, an important question for us to address is whether we can incorporate bispecifics into the treatment of newly diagnosed diffuse large B cell lymphoma to improve first-line cure fraction...
So, we recognize as a field the emerging importance of bispecific antibodies and improving clinical outcomes, and we’ve seen monotherapy in the multiple-relapse setting. We’ve seen combination approaches in the second line and beyond. Certainly, an important question for us to address is whether we can incorporate bispecifics into the treatment of newly diagnosed diffuse large B cell lymphoma to improve first-line cure fraction. One such effort that’s important to highlight is the so-called Olympia-3 trial. This is an effort looking at the bispecific antibody odronextamab approved by the European regulatory agencies in the treatment of relapsed large cell lymphoma. In here, we’re combining odronextamab plus CHOP chemotherapy with the intention of comparing that to our CHOP in a randomized fashion. The first step down this road was dose finding to ensure that we have the proper dose of odronextamab. There’s always been some uncertainty as to the optimal dosing strategy when combining bispecifics with chemotherapy and whether you can pursue lower dose options. In the part 1A here of Olympia-3, we did some dose escalation dose finding work comparing the lower dose and higher dose strategies. And what we found is that indeed here, the higher dose strategy seems to be more optimized given our limited data available from this early run-in effort, where we saw improved both quantitative results in terms of complete response rates with 100% CR rates seen in the small number of patients treated at the higher or full-dose odronextamab, as well as some biological correlatives that seem to reinforce the optimized dosing strategy of the full-dose odronextamab as we move into the planned randomization. We plan to move this dose into the RCT phase, hopefully in early 2026, and I look forward to seeing that part roll out as we try to move the field forward.
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