On December 12, 2022 Regeneron Pharmaceuticals reorted positive initial data from a pivotal Phase 2 expansion cohort evaluating investigational linvoseltamab (formerly REGN5458) at the 200 mg dose recommended for further development in patients with heavily pre-treated, relapsed/refractory (R/R) multiple myeloma (Press release, Regeneron, DEC 12, 2022, View Source [SID1234625126]). The results were part of a broader presentation of new and updated data from a Phase 1/2 trial and were shared at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, LA. 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 local T-cell activation and cancer-cell killing.

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"The need for innovative medicines is critical for patients with multiple myeloma who inevitably face a downward spiral of relapses, reduced responses to subsequent therapies, and increasingly shorter remissions," said Naresh Bumma, M.D., Hematologist and Assistant Professor in the Division of Hematology at Ohio State University, and a trial investigator. "At the recommended 200 mg dose in a pivotal Phase 2 trial, linvoseltamab demonstrated early, deep and durable responses in patients living with multiple myeloma who had been on at least three prior therapies, including those with higher risk and high disease burden. These clinically meaningful outcomes at 12 weeks reinforce the positive linvoseltamab results seen in the Phase 1 dose escalation portion, and we look forward to seeing data from more patients and longer follow-up."

As presented at ASH (Free ASH Whitepaper), out of 252 patients treated in the Phase 1/2 trial, 81% of patients were triple-refractory to existing therapeutic options, including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody. Additionally, 37% had bone marrow plasma cells ≥50%, and the median soluble BCMA was 0.43 mg/L, representing a patient population with a higher disease burden than those enrolled in similar trials. Of the 87 patients in the 200 mg cohort, 58 were evaluated for efficacy. With a median follow-up of 3 months (range: 0 to 30 months), efficacy results were as follows:

64% objective response rate (ORR), with 45% achieving a very good partial response or better, as determined by an independent review committee. Based on earlier results, responses may increase with longer follow-up.
Median time to response was <1 month (range: <1 to 5 months).
79% probability of maintaining a response at 6 months (95% confidence interval: 50% to 92%), per Kaplan-Meier estimates.
Among the 87 patients treated in the 200 mg cohort assessed for safety, adverse events (AEs) occurred in 95% of patients, with 66% being ≥Grade 3. The most common AEs occurring in ≥20% of patients were cytokine release syndrome (CRS; 37%), fatigue (32%), anemia (28%), diarrhea, cough, headache (23% each) and neutropenia (20%). Discontinuations due to an AE occurred in 6% of patients. When CRS occurred, in 32 out of 87 patients, 23 of those patients experienced Grade 1, 8 experienced Grade 2, there was 1 transient Grade 3 case, and none were ≥Grade 4.

Among the overall patient population across different dose levels (n=252), the median time to first CRS onset was 11 hours (range: 0-47 hours) and all cases resolved, with a median time to resolution of 15 hours (range: 0-377 hours). Deaths due to AEs in the overall population were reported in 14 patients, including sepsis/bacterial infection (n=6), COVID-19 (n=4) or other causes (n=4). None of the deaths were considered related to treatment per the treating physician.

Linvoseltamab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.