Regeneron Pharmaceuticals announced that the 14-month median follow-up data from the pivotal Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) were shared during an oral presentation at the European Hematology Association (EHA) Congress 2024 and published in the Journal of Clinical Oncology. These longer-term results show a deepening of responses following the 11-month median follow-up data presented at the American Association for Cancer Research Annual Meeting in April. Linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
“Previous results from LINKER-MM1 have demonstrated that linvoseltamab has compelling efficacy characterized by deep and durable responses. With 14 months of median follow-up, 50% of patients achieved a complete response or better, despite their cancer being refractory to or relapsing on standard therapies,” said Suzanne Lentzsch, MD, PhD, Director of the Multiple Myeloma and Amyloidosis Program at Columbia University. “Additionally, a study using US-based electronic health record data to indirectly compare linvoseltamab to real-world standard-of-care treatment also supports the overall body of evidence for this investigational medicine in heavily pretreated multiple myeloma. Collectively, these presentations underscore the exciting potential of linvoseltamab as we await decisions from regulatory authorities.”
The 14-month median follow-up LINKER-MM1 data for linvoseltamab among patients treated at the 200 mg dose (N=117) reinforces the durability and increasing depth of response shown in previous data cuts. Per the presentation and publication, results showed a 71% objective response rate (ORR), with 50% of patients achieving a complete response (CR) or better and 63% achieving a very good partial response (VGPR) or better, as determined by an independent review committee.
Linvoseltamab Shows Promising Long-Term Efficacy and Safety in Multiple Myeloma Trial
The median duration of response (DoR) was 29 months for all responders, while the median DoR was not reached for those who achieved a CR or better. In analyses that were not pre-specified, there was an 81% and 95% estimated probability of maintaining a response at 12 months after achieving a partial response or better among all patients and those who achieved a CR or better, respectively.
Median progression-free survival (PFS) was not reached, with a 70% estimated probability of being progression-free at 12 months among all patients and a 96% probability among those who achieved a CR or better. Median overall survival (OS) was 31 months for all patients. In analyses that were not pre-specified, the median OS was not reached for patients who achieved a CR or better, with a 75% and 100% estimated probability of survival at 12 months among all patients and those who achieved a CR or better, respectively.
High rates of CRs or better were observed in prespecified subgroups, including 55% among those aged 75 years or older, 48% among those with high cytogenetic risk, 45% among Black or African American patients, and 28% among those with plasmacytomas (including extramedullary and paramedullary). Safety data at the 14-month median follow-up were generally consistent with those at the 11-month median follow-up.
Adverse Events and Comparative Study Results in Multiple Myeloma Patients
Cytokine release syndrome (CRS) was the most commonly occurring treatment-emergent adverse event (TEAE), observed in 46% of patients, with 35% Grade 1, 10% Grade 2, and one caseGrade 3. Adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) events of any grade occurred in 8% of patients, including three cases of Grade 3 and no cases of Grade 4 or higher. Infections occurred in 74% of patients, including 36% that were Grade 3 or 4, with a decrease in frequency and severity after six months. The most common Grade 3 or 4 TEAEs were neutropenia (42%) and anemia (31%). Six deaths were considered due to TEAEs by investigators, with five due to infection and one due to renal failure.
A retrospective study comparing outcomes of linvoseltamab 200 mg Phase 2 patients in LINKER-MM1 at 14 months of median follow-up to those of real-world external control patients (N=101) who received standard-of-care (SOC) treatment in clinical practice was also presented. Patients receiving SOC treatment met similar inclusion/exclusion criteria to the LINKER-MM1 trial. Comparing linvoseltamab to SOC treatment, the ORR was 70% versus 32% (odds ratio [OR] 5.4), median PFS was 20 months versus 3 months (hazard ratio [HR]: 0.23), and median OS was not reached versus 12 months (HR: 0.40).
In the U.S., linvoseltamab has been granted Fast Track Designation and was accepted for Priority Review for the treatment of R/R multiple myeloma by the U.S. Food and Drug Administration with a target action date of August 22, 2024. Linvoseltamab is also under review for R/R multiple myeloma by the European Medicines Association. The Phase 3 confirmatory trial for linvoseltamab in patients with R/R multiple myeloma is ongoing. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
Resource: Regeneron, June 16, 2024
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