On December 12, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive first data from a cohort of a pivotal Phase 2 trial evaluating investigational odronextamab in patients with heavily pre-treated, relapsed/refractory (R/R) follicular lymphoma (FL) grades 1 to 3a (Press release, Regeneron, DEC 12, 2022, View Source [SID1234625141]). The data were presented in an oral session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, LA, and follow the first Phase 2 results for odronextamab in R/R diffuse large B-cell lymphoma (DLBCL) from the same trial that were presented yesterday. The results will form the basis of planned submissions to regulatory authorities in 2023, including to the U.S. Food and Drug Administration (FDA). Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

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"There is high unmet need for follicular lymphoma treatments that can improve tumor control and extend survival, given that there is no cure for this cancer and patients will experience multiple relapses," said Tae Min Kim, M.D., Ph.D., Department of Internal Medicine, Seoul National University Hospital in Seoul, South Korea, and a trial investigator. "These positive pivotal Phase 2 results investigating odronextamab in heavily pre-treated, relapsed/refractory follicular lymphoma patients showed deep and durable response – confirming earlier findings in this program – with the highest complete response rates seen in this patient population to date. We look forward to seeing the data continue to mature."

At ASH (Free ASH Whitepaper), efficacy in R/R FL was presented from 121 patients enrolled in a Phase 2 trial cohort (median follow-up: 22 months, range: 3-33 months). All patients had received at least two prior therapies, including a CD20 antibody and alkylating agent. Patients were treated with a step-up regimen of odronextamab in the first cycle to help mitigate the risk of cytokine release syndrome (CRS) before receiving the full dose of 80 mg. The step-up regimen was modified part way through the trial to further mitigate CRS. Results as assessed by independent central review were as follows:

82% objective response rate (ORR), with 75% achieving a complete response (CR). The median duration of complete response (mDOCR) was 20.5 months (95% confidence interval [CI]: 17 months to not evaluable [NE]).
Median progression-free survival was 20 months (PFS; 95% CI: 15 months to NE).
Median overall survival (OS) not reached (95% CI: NE to NE).
Among 131 patients assessed for safety, adverse events (AE) occurred in all patients, with 78% being ≥Grade 3. The most common AEs occurring in ≥20% of patients were CRS (56.5%), neutropenia (40%), pyrexia (31%), anemia (30%), infusion-related reaction (29%), arthralgia (21%), diarrhea (21%) and thrombocytopenia (20%). Discontinuations due to an AE occurred in 11.5% of patients, and there were 3 deaths due to pneumonia, progressive multifocal leukoencephalopathy and systemic mycosis where the relationship to odronextamab treatment could not be excluded.

CRS was the most common AE, of which 68% of cases were mild (Grade 1) and all resolved within a median of 2 days (range: 1-51 days). There were no Grade 4 or 5 CRS cases, and the incidence of both Grade 2 and Grade 3 was reduced with the modified step-up regimen when compared to the original regimen (original regimen n=68 vs. step-up regimen n=63; Grade 2: 18% vs. 11%, Grade 3: 6% vs. 2%).

Based on these data, the OLYMPIA Phase 3 development program investigating odronextamab is in the process of being initiated. In the U.S., odronextamab has been granted Fast Track Designation for FL by the FDA. In the European Union, Orphan Drug Designation was granted for FL by the European Medicines Agency. Odronextamab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.

Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Wednesday, December 14 at 8:30 AM ET. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

About the Trials
ELM-2 is an open-label, multicenter Phase 2 trial investigating odronextamab in more than 500 patients across five independent disease-specific cohorts, including FL, diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL). The primary endpoint is ORR according to the Lugano Classification, and secondary endpoints include CR, PFS, OS, duration of response, disease control rate, safety and quality of life.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy. Subcutaneous administration is being evaluated in two disease specific cohorts.

About Follicular Lymphoma (FL)
One of the most common subtypes of B-NHL, FL is a slow-growing (indolent) form of B-NHL with most cases diagnosed in advanced stages. Although median survival ranges from 8 to 15 years in advanced FL, current therapeutic options are not curative, and most patients relapse within five years regardless of the regimen. In some cases, FL can transform into DLBCL, at which point it is often treated in the same way as DLBCL.