7502 Background: Systemic AL amyloidosis is caused by deposition of misfolded amyloid fibrils produced by clonal plasma cells in vital organs. With no currently approved therapies, there is a need for new targeted agents eliciting rapid normalization of involved free light chain (iFLC), which is linked to improved organ function recovery and overall survival. Here are the first results of LINVO (human BCMA×CD3 bispecific antibody) in RR systemic AL amyloidosis from the Phase 1 portion of the Phase 1/2 LINKER-AL2 trial (NCT06292780). Methods: Eligible adults with RR systemic AL amyloidosis and ≥1 prior therapy received intravenous step-up doses of LINVO 5 mg and 25 mg (Cycle C 0 Days 1 and 8, respectively) followed by 28-day cycles of full subcutaneous (SC) doses of 80 mg or 240 mg administered once weekly in C1–C2 and then once every 4 weeks in C3–C12. The Phase 1 primary endpoint was incidence of dose-limiting toxicities (DLTs) within 28 days after the first full dose. Key secondary endpoints were rates of hematologic complete response (hCR; by FLC ratio and absence of AL), very good partial response or better (≥hVGPR), objective response (hOR), time to hCR, and safety. Results: As of data cut-off (DCO) August 25, 2025, 20 pts (median age, 64 years; prior daratumumab therapy, 60.0%) received LINVO 80 mg (n=7) or 240 mg (n=13), with a median follow-up of 9.6 (range 1.1–25.0) weeks. No DLTs or ICANS occurred. All pts had ≥1 treatment-emergent adverse event (TEAE; Grade (Gr) ≥3, 55.0%). One pt with prior cardiac disorder discontinued (Gr 5 ventricular fibrillation, unrelated to LINVO). Most common TEAEs were CRS (50.0%; Gr 1, 35.0%; Gr 2, 15.0%) and infusion-related reactions (45.0%; Gr 1, 25.0%; Gr 2, 20.0%), most during step-up dosing. LINVO elicited rapid responses (Table): hOR rates were 100% (80 mg: ≥hCR, 57.1%) and 92.3% (240 mg: ≥hCR, 38.5%), which are expected to deepen with longer follow-up. Most pts reached iFLC <20 mg/L (80 mg: 100%; 240 mg: 84.6%). Conclusions: LINVO demonstrated generally manageable safety and rapid, meaningful clinical activity, with most pts achieving hOR and iFLC <20 mg/L. These results support continued evaluation of LINVO in RR systemic AL amyloidosis. Longer follow-up data, including organ responses, are being evaluated. Clinical trial information: NCT06292780 . Investigator-assessed hematologic responses (ISA criteria). Response, n (%)* LINVO 80 mg (n=7) LINVO 240 mg (n=13) † Median follow-up, weeks (range) 12.1 (6.9–25.0) 6.7 (1.1–15.3) hOR 7 (100) 12 (92.3) hCR 4 (57.1) 5 (38.5) ≥hVGPR 7 (100) 12 (92.3) Low dFLC ‡ 0 1 (7.7) dFLC <10 mg/L 7 (100) 11 (84.6) iFLC <20 mg/L 7 (100) 11 (84.6) Median time to hCR, weeks (range) 3.2 (2.1–18.3) 3.1 (1.0–7.1) *Unless stated otherwise. † Not evaluable, n=1. ‡ If baseline dFLC ≥20 mg/L and <50 mg/L, response other than hCR reached with dFLC <10 mg/L. dFLC, difference between iFLC and uninvolved FLC; ISA, International Society of Amyloidosis.
Wechalekar et al. (2026) studied this question.