Regeneron presents follow-up data from pivotal Phase 1/2 LINKER-MM1 trial

Regeneron Pharmaceuticals announced that 14-month median follow-up data from the pivotal Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory multiple myeloma were shared during an oral presentation at the European Hematology Association 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 on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing. The 14-month median follow-up LINKER-MM1 data for linvoseltamab among patients treated at the 200 mg dose reinforce the durability and increasing depth of response shown in previous data cuts. Per the presentation and publication, results showed: 71% objective response rate, with 50% of patients achieving a complete response or better and 63% achieving a very good partial response or better, as determined by an independent review committee. Median duration of response of 29 months for all responders, while 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 was not reached. There was a 70% estimated probability of being progression free at 12 months among all patients; the estimated probability was 96% among those who achieved a CR or better, per an analysis that was not pre-specified. Median overall survival of 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, and there was 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 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. Safety data at the 14-month median follow-up was generally consistent with those at the 11-month median follow-up. Cytokine release syndrome was the most commonly occurring treatment-emergent adverse event and was observed in 46% of patients; 35% were Grade 1, 10% were Grade 2 and one case was Grade 3. Adjudicated immune effector cell-associated neurotoxicity syndrome events of any grade occurred in 8% of patients, including three cases that were Grade 3 and no cases that were greater than or equal to Grade 4. Six deaths considered due to TEAEs by investigators occurred on treatment or within 30 days of the last treatment dose; five were due to infection, and one was due to renal failure. Also shared at EHA was 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 who received standard-of-care treatment in clinical practice. Patients receiving SOC treatment also met similar inclusion/exclusion criteria to the LINKER-MM1 trial. Comparing linvoseltamab to SOC treatment, the ORR was 70% versus 32%, median PFS was 20 months versus 3 months, and median OS was not reached versus 12 months.