Leads Biolabs' LBL-034 Demonstrates 82.5% Response Rate in Relapsed/Refractory Multiple Myeloma at ASH 2025
Key Insights
Leads Biolabs (search) presented Phase I/II data for LBL-034, a GPRC5D (search)/CD3 (search) bispecific antibody, showing an 82.5% overall response rate in relapsed/refractory multiple myeloma (search) patients.
The therapy demonstrated strong efficacy across difficult-to-treat subgroups, including 100% response rate in extramedullary disease (search) patients at the highest dose level.
LBL-034 showed a favorable safety profile with no dose-limiting toxicities up to 1200 μg/kg and predominantly mild adverse events.
Nanjing Leads Biolabs (search) presented compelling Phase I/II clinical data for LBL-034, a novel GPRC5D (search)/CD3 (search) bispecific antibody, at the 67th Annual Meeting of the American Society of Hematology (search) (ASH) in Orlando, Florida. The study, conducted across 17 centers in China under the leadership of Professor Jin Lu of Peking University People's Hospital, demonstrated an overall response rate of 82.5% in patients with relapsed/refractory multiple myeloma (search) (RRMM).
Strong Efficacy Across Dose Levels
LBL-034 showed robust anti-tumor activity across dose levels from 400-1200 μg/kg in 40 patients. The therapy achieved an overall response rate (ORR) of 82.5%, with 52.5% of patients achieving complete response or better (≥CR), 72.5% achieving very good partial response or better (≥VGPR), and 80.0% achieving minimal residual disease (MRD) negativity.
At the 800 μg/kg dose level, response rates were even more impressive, with ORR reaching 90.9% and complete response rate achieving 63.6%. These results highlight the dose-dependent efficacy of the bispecific antibody across the evaluated range.
Breakthrough Activity in Challenging Patient Populations
LBL-034 demonstrated particularly noteworthy efficacy in difficult-to-treat RRMM subgroups. In patients with extramedullary disease (search) (EMD), the therapy achieved a 75.0% overall response rate, including two stringent complete responses. At the highest dose of 1200 μg/kg, the response rate in EMD patients reached 100%, with rapid regression of extramedullary lesions observed.
The therapy also showed strong activity in patients previously treated with BCMA (search)-targeted therapies, achieving an 85.7% overall response rate with 57.1% achieving complete or stringent complete response. This finding is particularly significant given the limited treatment options available for patients who have progressed on BCMA-directed therapies.
Favorable Safety Profile
The safety analysis revealed that LBL-034 could be safely escalated to 1200 μg/kg with no dose-limiting toxicities (DLTs) or maximum tolerated dose (MTD) reached. Adverse events that impacted quality of life were predominantly Grade 1-2 and occurred mainly during the first treatment cycle, with markedly lower incidence in subsequent cycles.
Notably, taste, skin, and nail toxicities were infrequent and generally self-resolving, distinguishing LBL-034's safety profile from other T-cell engager therapies in this class.
Durable Clinical Benefit
The durability analysis showed promising long-term outcomes, with a 12-month progression-free survival (PFS) rate of 61.2% across the 400-1200 μg/kg dose range at a median follow-up of 9.6 months. At the 400 μg/kg dose level, where median follow-up reached 13.1 months in 11 patients, the 12-month PFS rate was 56.8%.
Advancing Clinical Development
Dr. Charles Cai, Chief Medical Officer of Leads Biolabs (search), emphasized the significance of these results: "We are delighted that the strong efficacy and clinical potential of LBL-034 have been recognized by the international scientific community."
The company is currently conducting a Phase II trial evaluating LBL-034 at the recommended Phase 2 dose of 1200 μg/kg across four distinct patient populations: fourth-line or later RRMM, second-line or later RRMM with extramedullary disease (search), fourth-line or later RRMM with prior BCMA (search) therapy, and relapsed/refractory plasma cell leukemia (search).
Novel Therapeutic Design
LBL-034 is engineered with a unique 2:1 binding format featuring two GPRC5D (search) binding sites and one CD3 (search) binding site, developed using Leads Biolabs (search)' proprietary LeadsBody platform. This design enables selective targeting of GPRC5D-positive cancer cells while conditionally activating T cells, potentially reducing cytokine release risk and minimizing systemic toxicity.
According to Frost & Sullivan, as of November 2024, LBL-034 represents the second most clinically advanced GPRC5D (search)-targeted CD3 (search) T-cell engager globally. The therapy received Orphan Drug Designation from the U.S. FDA in October 2024 for multiple myeloma (search) treatment.