Image credit: LASZLO | stock.adobe.com
Findings from the Phase II MagnetisMM-3 trial (NCT04649359) showed a significant survival benefit with Elrexfio (elranatamab-bcmm) in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM).1 Elrexfio, a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody, was granted accelerated approval by the FDA in August 2023 to treat patients with RRMM who were previously administered at least four lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.2
“These compelling overall survival data support the clinical benefit Elrexfio has already demonstrated and its potential to be a transformative treatment option for people with multiple myeloma,” Roger Dansey, MD, chief development officer, Oncology, Pfizer, said in a press release. “The latest results from MagnetisMM-3 reinforce the very promising efficacy observed with Elrexfio in a relapsed or refractory setting, with deep and durable responses and although definitive conclusions cannot be drawn across studies, the longest reported median progression-free survival among B-cell maturation antigen bispecific antibodies.”1
Elrexfio was designed to link to BCMA, which is highly expressed on the surface of MM cells. The CD3 receptor on the surface of T-cells then connects and activates them to kill myeloma cells. The binding affinity of Elrexfio for BCMA and CD3 was developed to enduce potent T-cell mediated anti-myeloma activity.3
The open-label, multicenter, non-randomized MagnetisMM-3 trial evaluated Elrexfio monotherapy in patients with MM who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-cluster of differentiation 38 antibody. Investigators enrolled one cohort of patients who were previously administered treatment with a BCMA-directed antibody drug conjugate or chimeric antigen receptor T-cell therapy and a cohort of patients who were not previously treated with those therapies.
Patients were administered subcutaneous Elrexfio in a pair of step-up priming doses followed by a weekly 76 mg injection. The trial’s primary endpoint is objective response rate as assessed by Blinded Independent Central Review (BICR), with key secondary endpoints that included duration of response (DOR), progression-free survival (PFS), minimal residual disease negativity rate, overall survival (OS), and safety.
The results show a median OS of 24.6 (95% CI, 13.4, NE) months (n=123) in the single-arm trial. Across more than two years of follow-up, the overall response rate (ORR) in the Elrexfio cohort was 61.0%, with a complete response (CR) rate of 37.4%. Investigators found that the responses deepened as the trial progressed, with median DOR not yet reached.
At two years, the estimated DOR rate was 66.9% (95% CI: 54.4, 76.7) among all responders and 87.9% (95% CI: 73.1, 94.8) among those who achieved CR or better response. Median PFS was 17.2 months (95% CI: 9.8 months-NE), whereas in patients achieving a CR or better response, median PFS was not yet reached, with an estimated PFS rate of 90.6% (95% CI: 76.9, 96.4) at two years.
In terms of safety, the profile of Elrexfio was consistent with reporting from prior clinical trials. Secondary primary malignancies (SPMs) occurred in five patients (4.1%), all of which were squamous cell carcinoma of the skin. This is consistent with SPMs that are frequently reported in patients with MM, according to the investigators, and there were no hematological SPMs reported.
“People with [RRMM] often have limited therapeutic options as their disease progresses due to treatment resistance, resulting in increasingly shorter remission and duration of response,” clinical trial investigator Mohamad Mohty, MD, PhD, professor of Hematology and head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France, said in a press release. “These impactful [OS] data are particularly encouraging given the very advanced patient population with characteristics associated with poorer outcomes.”1
References
1. ELREXFIO™ Shows Median Overall Survival of More Than Two Years in People with Relapsed or Refractory Multiple Myeloma. News release. Pfizer. June 14, 2024. Accessed June 14, 2024. https://www.pfizer.com/news/press-release/press-release-detail/elrexfiotm-shows-median-overall-survival-more-two-years
2. Pfizer’s ELREXFIO™ Receives U.S. FDA Accelerated Approval for Relapsed or Refractory Multiple Myeloma. News release. Pfizer. August 14, 2023. Accessed June 14, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfiotm-receives-us-fda-accelerated-approval
3. Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance. News release.Pfizer February 22, 2023. Accessed June 14, 2024. https://investors.pfizer.com/Investors/News/news-details/2023/Pfizers-Elranatamab-Receives-FDA-and-EMA-Filing-Acceptance/default.aspx.
