Leads Biolabs' LBL-024, a bispecific antibody targeting PD-L1 and 4-1BB, has received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of neuroendocrine cancer. This designation underscores the potential of LBL-024 to address a critical gap in the therapeutic landscape for this rare and aggressive malignancy. The ODD follows a Breakthrough Therapy Designation granted by China's National Medical Products Administration (NMPA).
LBL-024 is a tetravalent bispecific antibody designed to simultaneously block the PD-1/PD-L1 immunosuppressive pathway and selectively stimulate 4-1BB, a T-cell costimulatory protein, within the tumor microenvironment. This dual mechanism aims to enhance the immune system's ability to recognize and destroy tumor cells.
Clinical Evidence and Ongoing Trials
Clinical data from a phase 1/2 trial (NCT05170958) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated promising results for LBL-024 in patients with advanced extrapulmonary neuroendocrine cancers (EP-NEC) who had progressed on prior standard-of-care therapy. The study, which included patients aged 18 years and older with an ECOG performance status of 0 or 1 and adequate organ function, showed an objective response rate (ORR) of 33.3% among patients with advanced EP-NEC who underwent at least one tumor assessment (n = 45). All responders experienced a partial response (PR), and the disease control rate (DCR) was 51.1%.
In the overall population (n = 47), the PR rate was 31.9%, the stable disease rate was 17.0%, and the progressive disease rate was 46.8%. When evaluating the recommended phase 2 dose (RP2D) of 15 mg/kg, the ORR was 33.3% and the DCR was 48.5%. At a median follow-up of 8.5 months, the median duration of response (DOR) was 5.3 months. Notably, PD-L1 expression did not appear to influence the benefit from LBL-024.
As of July 2024, a single-arm pivotal trial of LBL-024 for EP-NEC is ongoing, marking it as the first 4-1BB-targeted drug candidate globally to have reached the pivotal stage. Additionally, a phase 1b/2 trial (NCT06157827) is underway, evaluating LBL-024 in combination with etoposide plus cisplatin or carboplatin as a first-line treatment for EP-NEC.
Safety Profile
The safety profile of LBL-024, based on data from 175 treated patients, showed that treatment-emergent adverse events (TEAEs) were common (92.0%), with treatment-related AEs (TRAEs) occurring in 77.1% of patients. Serious TEAEs and TRAEs were reported in 33.1% and 16.6% of patients, respectively. Grade 3 or higher AEs occurred in 39.4% of patients, with grade 3 or higher TRAEs in 20.6%. Dose interruptions and treatment discontinuation due to TRAEs were observed in 22.3% and 4.0% of patients, respectively. The most common TEAEs included anemia, increased aspartate aminotransferase, and increased alanine aminotransferase.
Significance of Orphan Drug Designation
The FDA's Orphan Drug Designation provides several benefits, including tax credits for clinical trial expenses, FDA guidance on clinical research, exemption of application fees, and seven years of market exclusivity upon approval. This designation is intended to encourage the development of therapies for rare diseases, such as neuroendocrine cancer, which affects an estimated 127,652 new cases in the United States each year.
"The receipt of ODD for LBL-024 from FDA represents a pivotal milestone in our global strategy," said Dr. Xiaoqiang Kang, founder, chairman, and CEO of Leads Biolabs. "This designation not only enables LBL-024 to receive additional policy support and resource allocation during its development, accelerating its path to market and positioning it as a potential first-in-class therapeutic antibody targeting 4-1BB worldwide, but also provides us with greater market opportunities and avenues for growth on a global scale."
