Regeneron Pharmaceuticals has announced promising initial results from its Phase 1b LINKER-MM2 trial evaluating linvoseltamab in combination with two different proteasome inhibitors (PIs) – carfilzomib and bortezomib – in patients with relapsed/refractory (R/R) multiple myeloma (MM). The data, which will be presented in two oral presentations at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting on June 2, showed high response rates in both combination regimens.
Impressive Response Rates with Carfilzomib Combination
The linvoseltamab-carfilzomib combination demonstrated particularly strong efficacy in patients with R/R multiple myeloma. Among 21 patients evaluable for efficacy, the treatment achieved a 90% objective response rate (ORR), with 76% of patients achieving a complete response (CR). With a median follow-up of 15 months, the estimated probability of maintaining a response at 12 months was 87%, and the probability of remaining progression-free was 83%.
All treated patients (n=23) had previous exposure to proteasome inhibitors, and more than half were refractory to at least one PI. The patient population included those with high-risk features – 48% had baseline soft tissue plasmacytomas, and 39% were over 75 years old.
"In clinical trials, treatment with linvoseltamab monotherapy in later-line settings generated impressive response rates, warranting investigation in earlier lines as well as in combination with other cancer therapies," said Salomon Manier, M.D., Ph.D., Professor of Hematology at Lille University Hospital in France. "While early, these compelling results for linvoseltamab combination therapy demonstrated high rates of clinical activity, even amongst those with previous exposure to the proteasome inhibitors evaluated in the cohorts."
Promising Results with Bortezomib Combination
The second cohort evaluating linvoseltamab in combination with bortezomib also showed promising clinical activity. Among 20 patients evaluable for efficacy, with a median follow-up of 9 months, the treatment achieved an 85% ORR, with 50% of patients achieving a CR. More than half of the enrolled patients (n=24) were refractory to PIs, including 58% to carfilzomib and 13% to bortezomib.
Safety Profile
Both combinations showed manageable safety profiles, though with notable adverse events. In the carfilzomib cohort, the most common treatment-emergent adverse events (TEAEs) of any grade included neutropenia (65%), cytokine release syndrome (CRS; 61%), diarrhea (52%), and thrombocytopenia (52%). Serious adverse events occurred in 83% of patients.
Similarly, in the bortezomib cohort, common TEAEs included CRS (58%), neutropenia (54%), and thrombocytopenia (54%). Four patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Two patients died due to adverse events: one from pneumonia deemed treatment-related and another from COVID-19 deemed unrelated to treatment.
Advancing Clinical Development
Based on these promising results, Regeneron is planning a registrational, randomized Phase 3 trial investigating the linvoseltamab-carfilzomib combination against standard-of-care in the same setting.
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. It is already approved in the European Union as Lynozyfic™ for adults with R/R MM that has progressed after at least three prior therapies. In the U.S., the FDA is reviewing the Biologics License Application for linvoseltamab with a target action date of July 10, 2025.
Multiple Myeloma: A Significant Unmet Need
Multiple myeloma remains the second most common blood cancer, with over 187,000 new cases diagnosed globally every year. In the U.S. alone, more than 36,000 new cases are expected to be diagnosed in 2025, with approximately 12,000 deaths anticipated.
The disease is characterized by the proliferation of cancerous plasma cells that crowd out healthy blood cells in the bone marrow, infiltrate other tissues, and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable, and most patients will ultimately experience cancer progression and require additional therapies.
Broad Clinical Development Program
Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy and in combination regimens across different lines of therapy in MM, including earlier lines of treatment and plasma cell precursor disorders.
In addition to LINKER-MM2, Regeneron is conducting several other trials, including LINKER-MM1 (Phase 1/2 monotherapy in R/R MM), LINKER-MM3 (Phase 3 confirmatory trial), LINKER-MM4 (Phase 1/2 in newly diagnosed MM), and studies in high-risk smoldering MM and other related conditions.
The uses of linvoseltamab in combination with either carfilzomib or bortezomib in patients with R/R MM are investigational and have not been approved by any regulatory authority.
