Shots:
- Recently, Regeneron presented Odronextamab’s data in treating patients with different B-NHL subtypes (OLYMPIA studies) and marginal zone lymphoma (ELM-2 study)
- Aafia Chaudhry, Vice President, Global Program Head for Hematology-Oncology at Regeneron, discusses Odronextamab’s ongoing studies as monotherapy and in combination to treat various malignancies
- Aafia shares the upcoming PDUFA date on July 30th for Odronextamab in R/R 3L+ FL
Saurabh: I’ve been really impressed by the complete response rate for previously untreated follicular lymphoma patients in the OLYMPIA-1 trial. How does this stack up against what we’ve seen historically with our standard treatments?
Aafia: The Phase 3 OLYMPIA-1 trial is designed to explore odronextamab, a novel, fixed duration treatment in the outpatient setting, in patients with previously untreated follicular lymphoma (FL). In the most recent data shared at the 2024 American Society of Hematology (ASH) annual meeting, odronextamab led to complete responses (CR) in all 12 patients evaluable for efficacy at week 12 in Part 1 (N=13) of the study. Historical clinical trial data indicate that the standard-of-care, rituximab plus standard-of-care chemotherapies (R-Chemo) is associated with an objective response rate (ORR) of 89% and 67% CR rate. Our compelling, initial data show the potential of odronextamab in previously untreated patients and reinforce the remarkable complete response rates odronextamab has demonstrated in late-line FL.
The most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 62%), diarrhea (46%) and rash (39%). All cases of CRS were Grade 1. Infections occurred in 39% of patients, and 15% experienced a Grade 3 infection. Grade ≥3 TEAEs occurred in 46% of patients, which included one patient who discontinued early due to elevated liver enzymes.
Saurabh: Let’s talk about the ELM-2 trial. Those results for heavily pretreated marginal zone lymphoma patients look promising. What do you think this means for how we approach MZL treatment moving forward?
Aafia: Marginal zone lymphoma, or MZL, is another type of indolent B-cell non-Hodgkin lymphoma (B-NHL) that like follicular lymphoma, is often managed with chemo-immunotherapy in the front line setting with limited treatment options available to patients who relapse. The latest data from the ELM-2 trial presented at the ASH 2024 annual meeting shows compelling clinical efficacy in this patient population with a high unmet need.
- Among 42 enrolled patients, of which 35 patients were evaluable for efficacy, results at a median duration of follow-up of 11 months showed 77% ORR, with all responders achieving a CR, per investigator assessment. Among 42 patients evaluated for safety, the most common TEAEs (≥15%) were CRS (55%; all were Grade 1 or 2), infusion-related reaction (36%), pyrexia (36%) and neutropenia (31%).
The results underscore odronextamab as an important potential treatment option in the future management of relapsed/refractory (R/R) MZL. In addition to the ELM-2 trial, we are also evaluating odronextamab in MZL as a combination therapy in our OLYMPIA-5 confirmatory study which is currently underway.
Saurabh: I’m curious about the potential of odronextamab in earlier treatment lines, especially for follicular lymphoma. What are your thoughts on this?
Aafia: In clinical trials, treatment with odronextamab monotherapy in later-line settings generated compelling response rates, which warranted investigation in earlier lines. Given the indolent nature of the disease, there’s potential to explore various time-limited regimens, with the future option for retreatment in later lines. These hypotheses are being tested in our trials in the first-line setting – OLYMPIA-1 is evaluating odronextamab monotherapy versus R-chemo followed by two years of maintenance treatment, while OLYMPIA-2 is investigating odronextamab plus chemotherapy with or without maintenance.
Saurabh: Could you walk me through the ongoing OLYMPIA series of Phase 3 trials? I’m particularly interested in which B-NHL settings you’re evaluating.
Aafia: OLYMPIA is a broad Phase 3 clinical trial program investigating odronextamab in earlier lines of therapy and other B-NHL subtypes and includes:
OLYMPIA-1 evaluating odronextamab versus R-chemo in FL followed by two years of single-agent (odronextamab or rituximab) maintenance treatment.
OLYMPIA-2 evaluating odronextamab plus chemotherapy with and without odronextamab maintenance versus rituximab plus standard-of-care chemotherapies with or without rituximab maintenance in untreated FL. It is the only Phase 3 trial to investigate whether combining a CD20 bispecific with chemotherapy for 6 cycles is superior to R-chemo with rituximab maintenance
OLYMPIA-3 evaluating odronextamab plus a combination of chemotherapies called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) against rituximab plus CHOP in previously untreated diffuse large b-cell lymphoma, or DLBCL. Unlike other bispecific Phase 3 trials in untreated DLBCL, this is the only study comparing a CD20 bispecific combined with CHOP (without rituximab) head-to-head with R-CHOP
OLYMPIA-4 evaluating odronextamab compared to an investigator’s choice of standard-of-care regimens in previously treated aggressive B-NHL. This is the only study to be investigating a CD20 bispecific head-to-head vs standard of care transplant, which is critical for ensuring equitable access to off-the shelf therapies for transplant-eligible patients outside specialized centers.
OLYMPIA-5 evaluating odronextamab plus lenalidomide against rituximab plus lenalidomide in relapsed/refractory FL and MZL patients. This is one of the only Phase 3 trials exploring a CD20 bispecific in both indolent lymphoma settings.
Saurabh: Given how promising the results have been across different lymphoma subtypes, do you see any potential for combining odronextamab with other therapies present in the market?
Aafia: Yes – our broad OLYMPIA Phase 3 clinical trial program includes evaluating odronextamab in combinations with various approved regimens in various settings, including earlier lines of treatment. Additionally, the CLIO-1 trial is evaluating odronextamab in combination with our PD-1 inhibitor cemiplimab. Regeneron is also investigating novel combinations with odronextamab, including the ATHENA-1 trial evaluating odronextamab in combination with an investigational costimulatory CD22xCD28 bispecific antibody (REGN5837).
Saurabh: What’s next for odronextamab? Can you give us an idea of the upcoming steps in its clinical development? And when do you think we might see results from those larger Phase 3 trials?
Aafia: The target action date for FDA’s decision regarding approval of odronextamab in R/R 3L+ FL by the target action date of July 30, 2025.
Beyond R/R FL, we’re committed to investigating odronextamab in our broad and differentiated clinical program spanning several trials, indications and lines of treatment. Many of the Phase 3 trials are ongoing, and we plan to share results at future medical meetings.
About the Author:
Aafia Chaudhry
Aafia Chaudhry, MD, MBA, MS is the Vice President, Global Program Head for Hematology-Oncology at Regeneron Pharmaceuticals, Inc. In this role, Dr. Chaudhry is the strategic lead for the clinical development programs for lymphomas and myelodysplasia, which include bispecific antibodies, costimulatory antibodies, and other novel modalities. Her goal in this position is to harness science, strategy, and talent to advance patient-centered, transformative therapies.
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