FDA Grants Orphan Drug Designation to LBL-034 for Multiple Myeloma
核心洞察
The FDA has granted orphan drug designation to LBL-034 for treating multiple myeloma (搜索), a rare and life-threatening cancer.
LBL-034 is a humanized bispecific T-cell engager that targets GPRC5D (搜索) and CD3 (搜索), designed to activate T cells to kill myeloma cells.
A phase 1/2 clinical trial is currently evaluating LBL-034 in patients with relapsed/refractory multiple myeloma (搜索), showing promising early results.
The FDA has granted orphan drug designation to LBL-034, a humanized bispecific T-cell engaging antibody, for the treatment of multiple myeloma (搜索). This designation aims to support the development of LBL-034, which targets GPRC5D (搜索) and CD3 (搜索), for this rare and life-threatening cancer. The drug is currently in phase 1/2 clinical trials, with early data suggesting promising efficacy and a favorable safety profile.
Mechanism of Action
LBL-034 is designed to bind to CD3 (搜索) on T cells and GPRC5D (搜索) on myeloma cells, activating T cells to target and kill cancer cells. According to Leads Biolabs (搜索), LBL-034 demonstrates superior binding affinity for GPRC5D, increased potency, and a reduced risk of T-cell exhaustion and cell death compared with other agents in its class. Charles Cai, MD, PhD, chief medical officer of Leads Biolabs, stated that LBL-034 adopts a unique molecular design, and the preliminary clinical results indicate its promising antitumor efficacy and safety.
Clinical Trial Details
Currently, LBL-034 is being evaluated in a first-in-human, open-label, multicenter, dose-escalation and dose-expansion phase 1/2 trial (NCT06049290) in patients with relapsed/refractory multiple myeloma (搜索). The trial, which received IND approval from both the Chinese National Medical Products Administration and the FDA in July 2023, was launched in China in 2023. The study consists of a phase 1 dose-escalation and dose-expansion study, followed by a phase 2 efficacy study. The phase 1 study assesses the safety and tolerability of LBL-034 and determines the recommended phase 2 dose. The phase 2 study evaluates the efficacy of LBL-034 in treating relapsed/refractory multiple myeloma and includes 2 treatment arms. The trial aims to enroll between 66 and 418 patients across both phases.
Enrollment is open to patients aged 18 years and older with an ECOG performance status of 0 or 1, documented initial diagnosis of multiple myeloma (搜索) according to International Myeloma Working Group diagnostic criteria, and a life expectancy of at least 12 weeks. The primary end points of the study include objective response rate, dose-limiting toxicities, and maximum tolerated dose. The secondary end points are pharmacokinetics, immunogenicity, minimal residual disease, and duration of response. Preliminary results are expected to be presented at the 2024 ASH Annual Meeting & Exposition.
Preclinical Data
Preclinical studies presented at the 2023 ASH Annual Meeting demonstrated robust T-cell dependent cytotoxicity in GPRC5D (搜索)-positive cells across a range of expression levels, as well as increased expression of CD25 and CD69 and cytokine release, including IFN-γ, TNF-α, IL-6. Notably, LBL-034 exhibited minimal binding to CD3 (搜索) and limited cytokine release in the absence of GPRC5D-expressing cells. In additional preclinical models, LBL-034 showed potent antitumor activity even at low doses, including 1 mg/kg in the MC38-GPRC5D syngeneic model and 0.3 mg/kg in the NCI-H929 xenograft model.
Toxicology studies have also revealed that repeated intravenous doses of LBL-034 at 5 mg/kg, 15 mg/kg, and 50 mg/kg, administered weekly for up to 5 cycles, were well tolerated. Pharmacological, pathological, and biochemical analyses determined the no-observed-adverse-effect-level of LBL-034 to be 50 mg/kg.
Company Statement
Xiaoqiang Kang, MD, PhD, founder, chairman, and chief executive officer of Leads Biolabs (搜索), added that LBL-034 is the first product from Leads Biolabs to receive orphan drug designation from the FDA, marking a successful step for the company. He stated that they will further optimize their pipeline layout, broaden their exploration boundaries in the biopharmaceutical field, and provide innovative solutions for more unmet medical needs.