Amog sufferers with beforehand untreated diffuse massive B-cell lymphoma (DLBCL), therapy with the CD20 and CD3 bispecific antibody odronextamab has been related to early efficacy together with customary CHOP chemotherapy.
The primary outcomes from a small cohort of sufferers enrolled partly 1 of the part 3 OLYMPIA-3 research have been introduced on the 2025 ASH Annual Assembly.
Within the early outcomes, the target response charge (ORR) was 78% with the weekly 80 milligram dose of odronextamab plus CHOP and was 100% for the weekly 160 milligram dose of odronextamab plus CHOP. The whole response charges have been 44% and 100% for every dose, respectively. The median length of response, length of full response and progression-free survival weren’t but reached on the early evaluation. Primarily based on the mix of efficacy and security, the 160 milligram dose of odronextamab was chosen for additional investigation within the randomized portion of the research evaluating the bispecific with Rituxan (rituximab).
Glossary
Goal Response Price (ORR): the proportion of sufferers whose tumors shrink or disappear after therapy.
Development-Free Survival (PFS): the size of time throughout and after therapy when the most cancers doesn’t develop or unfold.
ECOG Efficiency Standing: a scale medical doctors use to explain how nicely an individual is ready to carry out each day actions.
Neutropenia: a drop in neutrophils, a sort of white blood cell that fights an infection.
Cytokine Launch Syndrome (CRS): a response that may occur when the immune system turns into very energetic throughout sure therapies, like immunotherapy. Signs could embrace fever, fatigue, or low blood stress.
Anemia: a situation by which the physique has too few crimson blood cells.
“Information from half 1a of OLYMPIA-3 counsel that when combining odronextamab with CHOP in beforehand untreated sufferers with DLBCL, [Rituxan] was not required to realize deep and sturdy responses,” lead investigator Dr. Jean-Marie Michot from Institute Gustave Roussy, stated throughout a presentation of the outcomes. “The security profile of mounted length odronextamab-CHOP therapy was typically manageable in sufferers with beforehand untreated DLBCL with high-risk options, with no new security indicators in contrast with earlier studies.”
OLYMPIA-3 Research Design and Affected person Traits
The open-label research was designed with two elements. Partially 1, the dose of odronextamab was escalated and optimized. Commonplace CHOP was given on day 1 and eight of every cycle and odronextamab was administered beginning on day 8, initially at a step-up dose of 0.7/4/20 milligrams after which at various dose ranges together with 80 milligrams or 160 milligrams weekly and 160 milligrams and 320 milligrams each two weeks, with knowledge solely accessible for the weekly doses. Half 2 of the research will proceed CHOP with sufferers randomly assigned to obtain odronextamab (Odro-CHOP) or Rituxan(R-CHOP).
Throughout all of half 1, the median age of sufferers was 66 years, with almost a 3rd aged 75 or older (32%). ECOG efficiency standing was 0 (40%), 1 (45%) and a couple of (14%). The first cell of origin was non-GCB (59%), and all sufferers had de novo DLBCL. IPI rating was 3 for 36% and 4 to five for 27% of sufferers. The Lugano stage was 3 to 4 for 95% of sufferers.
On the time of the evaluation, 77.8% of sufferers enrolled to the 80 milligram dose had accomplished cycle 1 to six (seven of 9). The rest of sufferers on this group had discontinued early, as a consequence of doctor determination (two sufferers). Within the 160-mg arm (13 sufferers), all sufferers had accomplished cycle 1 and 84.6% had accomplished cycle 6. Two discontinued early as a consequence of doctor determination. The relative dose depth was 87% within the 80-milligram group and 77% within the 160- milligram group.
“Most sufferers accomplished six cycles of odronextamab-CHOP at each dose ranges,” stated Michot. “There have been few dose reductions of odronextamab and no everlasting therapy discontinuations as a consequence of [treatment-emergent side effects] associated to odronextamab. There have been no clinically necessary variations in security between dose ranges.”
Further Odronextamab Efficacy Findings
The median length of follow-up was 9.2 months for these enrolled within the 80 milligram dose and was 7.8 months for these within the 160 milligram dose. On the evaluation, most responses remained ongoing. “CRs appeared sturdy,” Michot stated.
In a biomarker evaluation, B cell counts declined shortly following the initiation of remedy. There was an preliminary drop with CHOP administration, with B cells being utterly cleared with the initiation of odronextamab.
There was slight T cell margination following the initiation of remedy, however these have been transient and like prior studies with odronextamab, Michot stated. T cell findings have been comparable for every dose.
Odronextamab Security Profile in OLYMPIA-3
Grade 3 (extreme) or increased therapy emergent unwanted side effects have been skilled by all sufferers handled with the 80 milligram and 160 milligram doses of odronextamab. Critical therapy emergent unwanted side effects have been seen in 77.8% of these handled with the 80 milligram dose and for 92.3% of these administered the 160 milligram dose. Remedy emergent unwanted side effects led to therapy interruption or delay for 66.7% of these within the 80-milligram arm and for 84.6% of these within the 160-milligram group.
Remedy emergent unwanted side effects led to an odronextamab dose discount for no sufferers within the 80 milligram arm and for one within the 160-milligram group. Dose reductions in CHOP as a consequence of therapy emergent unwanted side effects have been wanted for one affected person within the 80-milligram group and for 5 within the 160-milligram group. Remedy emergent unwanted side effects led to therapy discontinuation for one affected person in every dose degree arm. There was one therapy emergent facet impact that led to loss of life within the 160-milligram arm. “Of be aware, there have been no dose-limiting toxicities reported,” Michot stated.
Throughout each doses, the commonest therapy emergent unwanted side effects have been neutropenia (81.8%), cytokine launch syndrome (CRS; 54.5%), anemia (45.5%) and nausea (40.9%). The commonest treatment-related unwanted side effects have been comparable with neutropenia seen in 77.3% of sufferers, CRS in 54.5%, anemia in 45.5% and nausea in 36.4%.
CRS was solely grade 1 (delicate)/2 (reasonable) in severity, with 40.9% of sufferers having a grade 1 occasion and 13.6% having a grade 2 occasion. Tocilizumab was administered to handle CRS for 27.3% of sufferers and steroids got for 18.2%. The median CRS length was 3.8 months and the median time to onset was 9 hours. CRS principally occurred through the step-up dosing part on the lowest dose of 0.7 mg, after this preliminary step-up the charges of CRS have been low. There have been no instances of immune effector cell–related neurotoxicity syndrome or tumor lysis syndrome.
Infections have been seen in 81.8% of sufferers handled throughout each ranges. Of those, 31.8% have been grade 3 in severity and 9.1% have been grade 4 (life-threatening). Opportunistic infections have been skilled by 50% of sufferers, of which just one affected person had a grade 3 or increased opportunistic an infection. Probably the most generally reported occasions have been CMV an infection or reinfection (27% for each) or COVID-19 and oral candidiasis (18% for every).
Odronextamab Regulatory Historical past and Additional Research
In August of 2025, the U.S. Meals and Drug Adminsitration (FDA) issued a whole response letter (CRL) for a biologics license software for odronextamab for the therapy of relapsed/refractory follicular lymphoma following two or extra strains of systemic remedy.Moreover, in March of 2024, the agent acquired two CRLs for DLBCL and follicular lymphoma. In each instances, the purposes have been based mostly on part 2 findings. The CRL issued in August famous considerations with website inspections accomplished at a plant ran by Catalent Indiana LLC.
Odronextamab is the topic of a number of scientific trials throughout a number of illness settings, both as monotherapy or in varied mixture regimens, together with the part 3 OLYMPIA-2 research for follicular lymphoma and the part 3 OLYMPIA-5 research taking a look at odronextamab plus lenalidomide for follicular lymphoma.
References:
- “Odronextamab plus chemotherapy in sufferers with beforehand untreated diffuse massive B-cell lymphoma (DLBCL): First Outcomes from half 1 of the Part 3 Olympia-3 research,” by Dr. Jean-Marie Michot et al., Blood.
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