A phase 1/2, first-in-human study showed that the investigational agent LBL-034 induced a response in 70.9% of patients (n=39/55) with relapsed/refractory multiple myeloma (MM).
The study was presented by Prof. Jin Lu, of Peking University People’s Hospital in Beijing, China, at the 67th ASH Annual Meeting and Exposition.
LBL-034 is a humanized IgG1 subtype asymmetric bispecific antibody targeting GPRC5D and CD3 with a 2:1 format.
The results of the ongoing open-label study include data from 56 patients (median age, 64 years; median number of prior lines of therapy, 5) who received intravenous LBL-034 at varying dose levels on days one and 15 of four-week cycles:
- 10 μg/kg (n=1)
- 30 μg/kg (n=1)
- 80 μg/kg (n=6)
- 200 μg/kg (n=7)
- 400 μg/kg (n=19)
- 800 μg/kg (n=11)
- 1200 μg/kg (n=11)
At the 80 μg/kg dose and above, researchers employed a step-up dosing strategy to mitigate cytokine release syndrome (CRS) risk.
Most patients were triple-class-exposed (69.6%) and penta-drug-exposed (57.1%); 16 patients (28.6%) received prior transplantation, and nine (16.1%) had received a BCMA-directed chimeric antigen receptor T-cell therapy.
Overall response rates (ORRs) varied by dose level among 55 evaluable patients:
- 200 μg/kg: 57.1%
- 400 μg/kg: 77.8%
- 800 μg/kg: 90.9%
- 1200 μg/kg: 81.8%
The ORR rate was “encouraging” at doses at or above 400 μg/kg even in “difficult-to-treat subgroups,” according to the authors, including 78.1% in penta-drug-exposed patients, 85.8% in patients who received BCMA-targeted therapy, and 75.0% in patients with extramedullary disease.
The median progression-free survival at doses at or above 200 μg/kg (n=47) was 11.7 months, with a median follow-up of 6.8 months.
Complete responses or better occurred in 14.3% at the 200 μg/kg dose, 55.6% at 400 μg/kg, 54.5% at 800 μg/kg, and 27.3% at 1200 μg/kg.
Measurable residual disease (MRD) negativity at 10-5 was achieved in 84.2% of evaluable patients (n=16/19). Median time to first complete response decreased with higher dose levels:
- 0 months at 400 μg/kg
- 4 months at 800 μg/kg
- 7 months at 1200 μg/kg
All patients experienced adverse events, including 83.9% who had grade ≥3 adverse events, the most common of which were:
- Lymphopenia (51.8%)
- Neutropenia (28.6%)
- Leukopenia (25.0%)
- Thrombocytopenia (17.9%)
- Anemia (16.1%)
Most patients (73.2%) experienced CRS, and one patient discontinued treatment due to an adverse event. There were no dose-limiting toxicities or dose reductions.
“These compelling efficacy and safety results strongly support the continued clinical development of LBL-034 in [relapsed/refractory] MM,” the authors concluded.
Reference
Dou X, Zhong Y, Zhao W, et al. A first-in-human, phase I/II, open-label, multicenter, dose escalation and expansion study of lbl-034, a conditionally activated bispecific antibody targeting GPRC5D and CD3 with a 2:1 format, in patients with relapsed/refractory multiple myeloma. Abstract #3972. Presented at the 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, Florida.
