Promising data for a novel, innovative bispecific antibody in MM

A novel investigational bispecific antibody with a unique mechanism of action demonstrated encouraging anti-tumour activity in patients with heavily pre-treated multiple myeloma (MM). According to the investigators, the molecule’s rational design likely contributed to its favourable safety profile.

“The investigational agent LBL-034 targets G protein-coupled receptor, family C, group 5, member D (GPRC5D) and CD3 in a 2:1 configuration, incorporating an affinity-optimised and sterically hindered anti-CD3 arm to reduce bystander T-cell engagement,” explained Prof. Jin Lu (Peking University People’s Hospital, China) [1]. The phase 1/2 trial LBL-034-CN001 (NCT06049290) enrolled 56 participants with MM who had received ≥3 prior lines of therapy. “Most participants were penta-class exposed and had high-risk cytogenetics,” Prof. Lu noted. Participants received 1 of 5 dose levels of LBL-034, with the primary objective of evaluating safety.

LBL-034 was associated with haematologic treatment-emergent adverse events, most commonly decreased lymphocyte count (71.4%), decreased platelet count (64.3%), and anaemia (55.4%). Grade 3–4 events occurred in 55.4%, 17.9%, and 16.1% of these cases, respectively. “Non-haematologic adverse events were predominantly low-grade,” said Prof. Lu. Cytokine release syndrome occurred in 73.2% of the participants, though only 1.8% were grade 3 or 4. The most frequent non-haematologic grade 3–4 events were hypokalaemia (12.5%), upper respiratory tract infection (16.1%), and bacterial infection (21.4%).

After a median follow-up of 9.6 months, the overall response rate in the pooled cohort receiving the 3 highest dose levels was 82.5%. Notably, 52.5% of the participants achieved a complete response or a stringent complete response. Prof. Lu also highlighted a 12-month progression-free survival rate of 61.2% among participants exposed to 1 of the 3 highest dose levels.

“These compelling results strongly support the continued clinical development of LBL-034,” concluded Prof. Lu. “A phase 2 study evaluating the safety and efficacy of LBL-034 in 4 subpopulations of patients with pre-treated MM is currently ongoing.”

1. Dou XL, 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 91, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 9 December 202522 December 2025