Latest odronextamab data in relapsed/refractory follicular lymphoma showed compelling responses and overall maintenance of patient-reported outcomes.- Regeneron Pharma.

These data – which include updated efficacy, safety and patient-reported outcomes (PROs) – were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition from December 9 to 12 in San Diego, CA. 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.

“The odronextamab data presented at ASH in patients with relapsed/refractory follicular lymphoma showcase a strong profile across measures of efficacy, safety and health-related quality of life,” said Benoît Tessoulin, M.D., Ph.D., Nantes University Hospital, Nantes; CRCI2NA, Nantes University, Nantes, France, and a trial investigator. “As clinicians, our focus must remain patients’ wellbeing, along with favorable outcomes. For odronextamab, it is particularly encouraging to see the unprecedented clinical results complemented by patient-reported outcomes that show quality of life and functional measures are maintained overall. These presentations underscore the potential role of odronextamab as a future medicine that treats relapsed/refractory follicular lymphoma and may allow patients to maintain health-related quality of life during the course of their therapy.”

As shared at ASH, longer-term data from the Phase II odronextamab trial continued to confirm high rates of durable responses in patients with R/R FL. At a prespecified interim analysis that occurred when the first 80 patients had greater than 12 months of follow-up, results among 128 patients that were assessed by independent central review (ICR) demonstrated : i. 80% objective response rate (ORR), with 73% achieving a complete response (CR). ii. Median duration of response (DoR) was 23 months (95% confidence interval [CI]: 17 months to not estimable [NE]) and median duration of CR was 24 months (95% CI: 18 months to NE) with a 18-month median duration of follow-up for efficacy evaluable patients (95% CI: 15 to 28 months). iii. Median progression-free survival (PFS) in complete responders was 28 months (95% CI: 20 months to NE) and 21 months for all patients (95% CI: 17 to 28 months). iv. Median overall survival (OS) was not reached (95% CI: 32 months to NE).

The most common adverse events (AE) occurring in greater than 30% of patients were cytokine release syndrome (CRS; 56%), neutropenia (48%), pyrexia (36%), anemia (34%), COVID-19 (31%) and infusion-related reactions (31%).

In 60 patients that received the recommended step-up regimen, 57% experienced CRS. All cases were resolved with supportive measures, with a median duration of 2 days (range: 1 to 10 days). Among these patients, 45% (n=27) had Grade 1 CRS, 10% (n=6) had Grade 2 CRS, and 2% (n=1) had Grade 3 CRS. There was one Grade 2 immune effector cell-associated neurotoxicity syndrome event reported, which was not associated with CRS.

As presented during an oral session at ASH, patients with R/R FL treated with odronextamab in the ELM-2 trial completed three validated questionnaires aimed at measuring health-related quality of life (HRQoL), functioning and symptoms. Pre-specified analyses were conducted across six scales. Overall, patients reported generally good HRQoL, functioning and low symptom burden at baseline as assessed across several scales . Key findings through Week 50 showed: i. Overall maintenance of moderate to high levels of functioning and HRQoL without detriments to patient-reported symptoms based on an analysis of changes in PRO scores from baseline over time, as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. ii. Median time to definitive deterioration in physical function and lymphoma-specific symptoms was not reached (per EORTC QLQ-30 and Functional Assessment of Cancer Therapy Lymphoma subscale, respectively). In an individual patient-level analysis, more patients reported maintenance or clinically meaningful improvement in physical functioning and lymphoma-specific symptoms than deterioration at each assessment.

Odronextamab is currently under regulatory review for the treatment of R/R FL and diffuse large B-cell lymphoma (DLBCL) by the FDA, with a target action date of March 31, 2024, as well as by the European Medicines Agency (EMA). In the U.S., odronextamab has been granted Fast Track Designation by the FDA. In the European Union, odronextamab has been granted Orphan Drug Designation by the EMA.