The 14-month median follow-up data from the pivotal Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) was shared during an oral presentation at the European Hematology Association (EHA) 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 (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

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

The 14-month median follow-up LINKER-MM1 data for linvoseltamab among patients treated at the 200 mg dose (N=117) reinforce the durability and increasing depth of response shown in previous data cuts. Per the presentation and publication, results showed:

• 71% objective response rate (ORR), with 50% of patients achieving a complete response (CR) or better and 63% achieving a very good partial response (VGPR) or better, as determined by an independent review committee.
• Median duration of response (DoR) 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 (PFS) 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 (OS) of 31 months for all patients (95% CI: 22 months to NE). 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% (17 of 31 patients) among those aged 75 years or older, 48% (22 of 46 patients) among those with high cytogenetic risk, 45% (9 of 20 patients) among Black or African American patients, and 28% (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 (CRS) was the most commonly occurring treatment-emergent adverse event (TEAE) and was observed in 46% of patients; 35% were Grade 1, 10% were Grade 2 and one case (1%) was Grade 3. Adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) events of any grade occurred in 8% of patients, including three cases that were Grade 3 and no cases that were ≥Grade 4. Infections occurred in 74% 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 TEAEs (≥20%) were neutropenia (42%) and anemia (31%). 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 (N=105) in LINKER-MM1 at 14-months of median follow-up to those of real-world external control patients (N=101) who received standard-of-care (SOC) treatment in clinical practice (approximately 80 varied regimens). 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% (odds ratio [OR] 5.4), median PFS was 20 months versus 3 months (hazard ratio [HR]: 0.23), and median OS was not reached versus 12 months (HR: 0.40).

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.

The Phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in patients with R/R MM is ongoing. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

Source: Regeneron