By Won Seog Kim, MD
How can Odronextamab help patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)? I presented here the interim analysis data for the next one, monotherapy, in patients with relapsed refractory DLBCL, in general, in patients who had the prior two or more lines of treatment. The outcome is quite disappointing in this Odronextamab clinical trial.
The expected survivor was less than several months, and with the cytotoxic agent, we cannot have good until now. So here we, I'm presenting the other next monotherapy data. This is an open label phase 2 trial of Odronextamab, we have, right now, we have the CAR T cells but still more than half of the patient are failing with the CAR T cell therapies and even the patient are eligible, the cost is very high and the manufacturing process is quite complicated. Therefore, we need, definitely need off-the-shelf compound to treat, to treat this kind of patient Odronextamab is one of the options we can have in this patient settings.
Before, we treated this patient with chemotherapy or on a clinical trial basis, but the outcome was quite disappointing. But recent years, we have T-cell in this patient population. But as I mentioned before, the manufacturing process is quite complicated and many patients cannot wait until the infusion times because it takes 1 to 2 months at least to get the infusions. Therefore, we definitely need the off-the-shelf compound.
This study is a phase 2, open label, multi-center phase 2 trial. We have the step of regimens in cycle one because, this agent can induce cytokine release syndrome (CRS), to mitigate the kind of risk we are putting in the step of regimens, we are slowly increasing the dose from lower levels to high levels. With that, we avoid severe cytokine release syndrome (CRS). That's the point we can succeed it. And the treatment was to continue to achieved disease progression.
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Odronextamab a experimental bispecific antibody designed to connect CD20 on cancer cells with CD3-expressing T cells in order to enable local T-cell activation and cancer-cell eradication.
Regarding the Clinical Trials
The ELM-2 is an ongoing, open-label, multicenter Phase 2 trial exploring odronextamab in over 500 patients with DLBCL, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL). The primary endpoint according to the Lugano Classification is ORR, whereas subsidiary endpoints include CR, progression-free survival, overall survival, length of response, disease control rate, safety, and quality of life.
The ELM-1 is an ongoing, multicenter, open-label Phase 1 trial investigating the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies who have been previously treated with CD20-directed antibody treatment. Subcutaneous administration is currently being investigated in two cohorts with distinct diseases.
Regarding Diffuse Large B-cell Lymphoma (DLBCL)
DLBCL (Diffuse Large B-Cell Lymphoma), one of the most prevalent subtypes of B-NHL, is an aggressive form of B-NHL, with up to fifty percent of patients with advanced-stage illness progressing after first-line therapy (e.g., relapsing or becoming refractory to treatment). Patients with relapsed/refractory DLBCL have limited therapeutic options and a dismal prognosis.
In this trial, we confirmed higher efficacy. The overall response rate was almost 50% with a 30% complete response rate, and the response was quite durable. And even the efficacy was quite consistent in patient who failed prior CAR T cell treatment, that's quite encouraging one. The primary end point of this trial was the overall response rate based on the independent central review, and the secondary end point was as usual.
The adverse events of this compound are quite different from previous experiences with cytotoxic agents. The immune toxicity is one of the adverse event with special interest. We have cytokine related syndrome (CRS), over 50% of the patient, but majority of them was quite a manageable and with modification of this type of regimens, we can mitigate that severe cytokine risk syndrome (CRS) and no patient had needed a mechanical ventilator support or ICU care. And ICANS is one of the novel immunotoxins of special interest. In this case, the ICANS was very rare, just less than 5%, particularly after modification of the stable regimens; we had only 1 grade 2 ICANS out of 70 patients, so it's, it is quite manageable.
That Odronextamab is a bispecific monoclonal antibody with high efficiencies with over 50, almost 50% of overall response rate and quite durable, and the toxicity is quite manageable. Therefore, it is one of the good options in the patient who failed 2 or more lines of treatment. And we are planning to move into earlier lines of treatment through the phase 3 trial.
Won Seog Kim, MD, PhD - About The Author, Credentials, and Affiliations
Dr. Won-Seog Kim is in charge of the service for malignant lymphoma. He is a trial investigator and a professor of hematology and oncology at the Samsung Medical Center and the Division of Hematology-Oncology at Sungkyunkwan University in Seoul, South Korea. He is a very important part of the Korean Society of Hematology's lymphoma working group and collaboration for improved lymphoma survival (CISL). He is the current chairman of the lymphoma working group of the Korean Society of Hematology. He is also a founding member of the Asian Lymphoma Research Group (ALSG).
At Regeneron, we are developing therapies for patients with different blood malignancies and uncommon blood disorders using our patented VelociSuite® technology and more than three decades of biological experience.
Our study on blood cancer focuses on bispecific antibodies that are being examined as monotherapies, in combination with each other, and in conjunction with developing therapeutic modalities. Together, they provide us with unprecedented combinatorial flexibility for the development of personalized and potentially synergistic cancer therapies.
The research and collaborations to develop potential treatments for rare blood disorders include investigations into antibody medicine, gene editing and gene-knockout technologies, as well as exploratory RNA-approaches aimed at depleting abnormal proteins or inhibiting disease-causing cellular signaling.
Regeneron Pharmaceuticals - PIVOTAL ODRONEXTAMAB (CD20XCD3) PHASE 2 DATA IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA DEBUT AT ASH. Regeneron Pharmaceuticals, December 11, 2022