The Phase 1/2 LINKER-MM1 trial of linvoseltamab in patients with relapsed/refractory (R/R) multiple myeloma (MM) was announced at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego. 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 presentation of these pivotal results in an oral plenary session at AACR recognises the exciting potential of linvoseltamab to advance the treatment of multiple myeloma,” said Sundar Jagannath, M.D., Director of the Multiple Myeloma Center of Excellence at Tisch Cancer Center at Mount Sinai in New York City and a trial investigator. “In clinical trials, linvoseltamab treatment led to responses that occurred early, were durable and deepened over time – all critical efficacy measures for this heavily pre-treated patient population. Further, among patients who had at least 24 weeks of treatment, the majority achieved a very good partial response, enabling them to transition from every two-week to every four-week dosing. This is an important accomplishment that I’ve seen firsthand in my trial patients, and I eagerly anticipate the FDA decision expected this August.”

With an 11-month median duration of follow-up, the linvoseltamab data among 117 patients presented at AACR reinforce the strength of previously shared findings and included a:

71% objective response rate (ORR), with 46% of patients achieving a complete response (CR) or better and 62% achieving a very good partial response (VGPR) or better, as determined by an independent review committee.

1-month median time to response (range: <1-6 months). In responders, the median time to a VGPR or better was 3 months (range: <1-13 months) and to a CR or better was 8 months (range: 2-14 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%.

Among patients who had a CR or better and were minimum residual disease (MRD) evaluable, 93% (25 of 27 patients) were MRD negative at 10-5.

The trial included a response-adapted regimen that enabled linvoseltamab patients to shift to every four-week dosing if they achieved a VGPR or better and completed at least 24 weeks of therapy. In the dose expansion portion of the trial (n=105), of the patients who had at least 24 weeks of therapy at data cutoff, 90% (56 of 62) achieved a VGPR or better and were able to transition to every four-week dosing. Of the 29 patients who transitioned to the extended dosing regimen prior to achieving a CR, 48% (14 of 29) subsequently experienced a deepening of response to CR or better.

In addition, high ORRs were observed across prespecified subgroups – including high-risk and high-disease burden populations – as follows:

• 85% among Black or African American patients (17 of 20 patients)
• 71% among those aged 75 years or older (22 of 31 patients)
• 67% among those with high cytogenetic risk (31 of 46 patients)
• 62% among those with International Staging System stage III disease (13 of 21 patients)
• 53% among those with extramedullary plasmacytomas (10 of 19 patients)

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 73% of patients, with their frequency and severity decreasing after 6 months; 34% were Grade 3 or 4. The most common Grade 3 or 4 TEAEs (≥20%) were neutropenia (40%) and anaemia (31%). Six deaths occurred on treatment or within 30 days of the last treatment dose due to TEAEs; five were due to infection, and one was due to renal failure.

Linvoseltamab has been granted Fast Track Designation and was accepted for Priority Review for the treatment of R/R MM by the FDA, with a target action date of August 22, 2024. In addition, linvoseltamab is being reviewed by the EMA. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

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

Source: Regeneron