LINKER-MM1 study: Linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

• DOI: 10.1200/jco.2023.41.16_suppl.8006
• Publication Date: 2023-06-04T16:11:56Z
• Authors: Hans C. Lee; Naresh Bumma; Joshua Ryan Richter; Madhav V. Dhodapkar; James E. Hoffman; Attaya Suvannasankha; Jeffrey A. Zonder; Mansi R. Shah; Suzanne Lentzsch; Joseph J. Maly; Jing Christine Ye; Ka Lung Wu; Michelle DeVeaux; Dhruti Chokshi; Anita Boyapati; Anasuya Hazra; Karen Rodriguez-L...; Glenn Scott Kroog; Yariv J. Houvras; Sundar Jagannath
• Keywords: Refractory (planetary science); Clinical endpoint; Minimal Residual Disease

8006 Background: Linvoseltamab is a BCMA×CD3 bispecific antibody with encouraging efficacy and manageable safety profile in patients (pts) relapsed/refractory multiple myeloma (RRMM) (Bumma et al. ASH 2022). Two Phase (Ph) 2 full dose cohorts (50 mg 200 mg) the LINKER-MM1 (NCT03761108) trial were studied to optimize selection. Methods: Ph enrolled adults MM who progressed on/after ≥3 lines of therapy (LoT) including proteasome inhibitor (PI), an immunomodulatory drug (IMiD), anti-CD38 (Ab), or at least triple class (IMiD/PI/anti-CD38 Ab) refractory. A protocol amendment permitted pts during 4–12 wks on 50 escalate mg. Primary endpoint was objective response rate (ORR). Key secondary endpoints included duration (DoR) minimal residual disease status. Results: As 1 Sept 2022, 252 have (Ph 1: 73; 2: 179 [200 mg: 75; 104]). Median age 66 yrs (range 37–90), 12% had extramedullary plasmacytomas, high-risk cytogenetics, 37% bone marrow plasma cell percentage (BMPC) ≥50%. soluble BCMA concentration (sBCMA) 0.43 mg/L 0–10.2), median prior LoT: 5 1–16), 81% ≥triple Numerically higher observed 200mg, high burden subgroups; ORR 64% (200 cohort; n = 58, includes 12 pts) 50% 104). Subgroup analyses showed cohort versus for sBCMA ≥0.4 (52% vs 37%), BMPC > 67% (64% 35%) revised ISS stage III (71% 27%). DoR not reached both (median follow-up: 2.3 months mg], 4.7 [50 mg]). Probability maintaining 6 89% 85% mg). Eight escalated from mg; (75%) achieved response. Treatment-emergent adverse events (TEAEs) occurred 95% (Grade [Gr] ≥3: 66%) (n 87, 100% (Gr 80%) cohort. The most common TEAEs cytokine release syndrome [Gr 3: 1%]; 53% 2%]), fatigue 32% 0]; 33% 0]) anemia 28% 24%]; 40% 36%]). Grade ICANS (2%) pt (1%) leading treatment discontinuation 7% cohort) 8% pts. Infections 43% 26%) 59% 31%) Conclusions: better compared mg, burden. consistent across subgroups induced responses Safety doses. recommended linvoseltamab further development Updated data longer follow-up complete enrollment will be presented meeting. Clinical information: NCT03761108 .