FDA grants fast track designation to investigational bispecific T-cell engager LBL-034 for RRMM

On January 29, 2026, the U.S. Food and Drug Administration (FDA) granted fast track designation to LBL-034, an investigational G protein-coupled receptor class C group 5 member D (GPRC5D)/CD3 bispecific T-cell engager (BiTE), for patients with relapsed/refractory multiple myeloma (RRMM). LBL-034 features a novel asymmetric 2:1 bispecific format, with two binding sites for GPRC5D on tumor cells and one for CD3 on T cells, enabling high-avidity targeting of myeloma cells, with controlled T-cell activation. This design is intended to enhance antitumor efficacy while potentially mitigating immunotherapy-related toxicities, including cytokine release syndrome (CRS) and T-cell exhaustion, compared with first-generation BiTEs. 

The designation follows safety and efficacy data from an ongoing phase I/II study (NCT06049290) conducted in China, which were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. The phase I dose escalation trial investigated the intravenous administration of LBL-034 in patients with ≥3 prior lines of therapy (LoT). Preliminary results from 55 evaluable patients show an objective response rate (ORR) of 70.9%, with dose-dependent activity at ≥800 μg/kg. Measurable residual disease (MRD)-negativity (10^-5) was observed in 84.2% of patients achieving a complete response or better (≥CR). Efficacy outcomes were favorable across difficult-to-treat subgroups, including patients with extramedullary disease and prior BCMA therapy. Grade 3 treatment-emergent adverse events (TEAEs) were reported in 83.9% of patients and were mainly hematologic, with cytokine release syndrome (CRS) observed in 73.2% of patients (one Grade 3 event). No maximum tolerated dose (MTD) or dose-limiting toxicities (DLTs) were reported up to 1200 μg/kg of LBL-034.