KEY TAKEAWAYS
- This phase 1/2 study evaluated the efficacy and safety of two linvoseltamab Phase 2 dosage groups in MM patients.
- The study’s primary endpoint was ORR.
- The 200 mg dose of linvoseltamab demonstrated greater efficacy than the 50 mg dose across various MM patient subgroups, including high-risk cases.
Linvoseltamab, a bispecific antibody targeting BCMA and CD3, has demonstrated favorable efficacy and a manageable safety profile in patients (pts) with relapsed or refractory multiple myeloma (MM). The LINKER-MM1 study examined two Phase 2 dosage groups (50 mg and 200 mg) to inform dose optimization better. This report presented an in-depth comparative analysis of the outcomes from these two dosage cohorts.
In the LINKER-MM1 study, adult participants with multiple myeloma who had shown progression after a minimum of three lines of treatment, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies, were enrolled. The Phase 2 section also involved pts resistant to all three classes of these drugs. An amendment to the protocol allowed participants who exhibited progression between 4 to 12 weeks on the 50 mg dose to escalate to 200 mg. The primary endpoint was the objective response rate (ORR).
The study analyzed 221 pts for efficacy and safety, comparing a 200 mg dosage group (n=117) to a 50 mg dosage group (n=104). The patient demographics and disease characteristics varied: 26% aged 75 years or older in the 200 mg group compared to 16% in the 50 mg group; 29% non-White in both groups; 36% high-risk cytogenetics in 200 mg vs. 24% in 50 mg; 14% with extramedullary plasmacytomas in both; and 22% vs. 35% had bone marrow plasma cells at or above 50%. Median soluble BCMA levels were consistent at 377 ng/mL in both groups. Most pts were resistant to at least three drug classes (74% in 200 mg group and 88% in the 50 mg group). The median follow-up durations were 5.6 months for the 200 mg group and 7.7 months for the 50 mg group.
ORR was higher in the 200 mg group (71%) than in the 50 mg group (50%). Higher ORRs in the 200 mg cohort were also evident across various pre-defined subcategories, such as age, race, disease stage, and functional status, among others. Median progression-free survival (PFS) was 7.9 months in the 50 mg group and had not been reached in the 200 mg group. Dose escalation from 50 mg to 200 mg was performed in 8 pts, 75% of whom achieved a very good partial response (VGPR).
Treatment-related adverse events (TEAEs) were common but comparably distributed across the two cohorts. Cytokine release syndrome was the most frequently observed TEAE in both groups (200 mg: 45%; 50 mg: 55%). Other common TEAEs included cough, neutropenia, fatigue, diarrhea, anemia, and arthralgia. Opportunistic infections were more prevalent in the 200 mg cohort (8% vs 2%).
The 200 mg dosage of linvoseltamab outperformed the 50 mg dosage in terms of efficacy. High ORRs were observed with the 200 mg dose across various patient subgroups, including those with high-risk features and high tumor burden. Some pts who initially showed progression on the 50 mg dose responded positively upon escalation to 200 mg. Given the similar safety profiles for both dosages, the 200 mg should be the recommended dosage for subsequent investigations.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03761108
Richter, J. Evaluation of the efficacy and safety of two different linvoseltamab Phase 2 dose regimens: Results from LINKER-MM1.
