The Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) was highlighted at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego. Linvoseltamab, designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells, aims to activate T-cells to kill cancer cells.
- 71% objective response rate (ORR) was observed, with 46% of patients achieving a complete response (CR) or better and 62% achieving a very good partial response (VGPR) or better.
- The median time to response was 1 month, with the median time to a VGPR or better at 3 months and to a CR or better at 8 months.
- Median duration of response (DoR), median progression-free survival (PFS), and median overall survival (OS) were not reached. At 12 months, the estimated probability of maintaining a response was 78%, being progression-free was 69%, and survival was 75%.
- 93% of patients who achieved a CR or better and were minimum residual disease (MRD) evaluable were MRD negative.
A response-adapted regimen allowed patients achieving a VGPR or better after at least 24 weeks of therapy to transition to every four-week dosing, with 90% of eligible patients making this transition. Additionally, 48% of patients who transitioned to extended dosing before achieving a CR experienced a deepening of response to CR or better.
High ORRs were observed across various subgroups, including 85% among Black or African American patients, 71% among those aged 75 years or older, and 67% among those with high cytogenetic risk.
The most common treatment-emergent adverse event (TEAE) was cytokine release syndrome (CRS), observed in 46% of patients, with the majority being Grade 1 or 2. Infections occurred in 73% of patients, with 34% being Grade 3 or 4. The most common Grade 3 or 4 TEAEs were neutropenia (40%) and anaemia (31%).
Linvoseltamab has received Fast Track Designation and was accepted for Priority Review by the FDA, with a target action date of August 22, 2024. It is also under review by the EMA. The Phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in patients with R/R MM is currently underway.