RARE Daily

Updated Regeneron Data in Multiple Myeloma Show Deepening Response

June 17, 2024

Rare Daily Staff

Regeneron Pharmaceuticals said 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 show a deepening of responses compared to the previously reported 11-month medial follow up data.

The new data reinforce the durability and increasing depth of response shown in previous data cuts.  It showed a 71 percent objective response rate, with 50 percent of patients achieving a complete response or better and 63 percent achieving a very good partial response or better, as determined by an independent review committee.

The data were presented during an oral presentation at the European Hematology Association Congress 2024 and published in the Journal of Clinical Oncology.

Multiple myeloma is characterized by the proliferation of cancerous plasma cells (MM 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 while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

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.

The phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in patients with R/R MM is ongoing.

Median duration of response of 29 months for all responders, while median duration of response was not reached for those who achieved a complete response or better. In analyses that were not pre-specified, there was an 81 percent and 95 percent estimated probability of maintaining a response at 12 months after achieving a partial response or better among all patients and those who achieved a complete response or better, respectively.

Median progression-free survival was not reached. There was a 70 percent estimated probability of being progression free at 12 months among all patients; the estimated probability was 96 percent among those who achieved a complete response or better, per an analysis that was not pre-specified.

Median overall survival of 31 months for all patients (95 percent). In analyses that were not pre-specified, the median overall survival was not reached for patients who achieved a complete response or better, and there was a 75 percent and 100 percent estimated probability of survival at 12 months among all patients and those who achieved a complete response or better, respectively.

High rates of complete responses or better in prespecified subgroups, including 55 percent (17 of 31 patients) among those aged 75 years or older, 48 percent (22 of 46 patients) among those with high cytogenetic risk, 45 percent (9 of 20 patients) among Black or African American patients, and 28 percent (10 of 36 patients) among those with plasmacytomas (including extramedullary and paramedullary).

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 percent of patients; 35 percent were Grade 1, 10 percent were Grade 2 and one case (1 percent) was Grade 3.

Adjudicated immune effector cell-associated neurotoxicity syndrome events of any grade occurred in 8 percent of patients, including three cases that were Grade 3 and no cases that were ≥Grade 4. Infections occurred in 74 percent of patients – including 36% that were Grade 3 or 4 – and decreased in frequency and severity after 6 months.

The most common Grade 3 or 4 treatment-emergent adverse event (≥20 percent) were neutropenia (42 percent) and anemia (31percent). Six deaths considered due to treatment-emergent adverse events 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.

In the U.S., linvoseltamab has been granted Fast Track Designation and was accepted for Priority Review for the treatment of R/R MM 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 MM by the European Medicines Association.

“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 percent of patients achieved a complete response or better, despite their cancer being refractory to or relapsing on standard therapies,” said Suzanne Lentzsch, 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 support 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.”

Photo: Suzanne Lentzsch, director of the Multiple Myeloma and Amyloidosis Program at Columbia University

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