Qilu Pharmaceutical Shares Promising Phase Ia Study Results for GPRC5D/CD3-Targeting Antibody QLS32015

Jinan, China – At the 66th Annual Meeting of the American Society of Hematology (ASH), held in San Diego from December 7 to 10, Qilu Pharmaceutical unveiled preliminary results from the Phase Ia study of QLS32015, a groundbreaking bispecific antibody designed to treat relapsed/refractory multiple myeloma (RRMM). These findings highlighted the drug’s robust anti-tumour activity and favourable safety profile.

Revolutionary Mechanism of QLS32015

QLS32015 represents a novel humanized IgG1 T-cell retargeting bispecific antibody. By simultaneously targeting GPRC5D (a G protein-coupled receptor) and CD3, it bridges CD3-expressing T cells with GPRC5D-expressing tumour cells. This mechanism bypasses traditional MHC-TCR binding pathways, forming an immune synapse that activates T cells to destroy cancer cells efficiently.

About the Phase I Clinical Trial

The ongoing open-label Phase I trial (NCT05920876), spearheaded by Prof. Lugui Qiu from the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences, is designed to evaluate the safety and preliminary efficacy of QLS32015 in RRMM patients. The trial’s dose-escalation and expansion stages aim to identify dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).

Patients enrolled in the study receive QLS32015 as a monotherapy at doses ranging from 2 to 200 μg/kg, administered either weekly or biweekly. The study employs a combination of accelerated titration and Bayesian optimal interval strategies to refine dosing parameters.

Preliminary Results: Safety and Efficacy

As of August 31, 2024, the trial enrolled 13 patients with a median age of 61 years. These individuals had undergone a median of three prior lines of therapy (range: 1 to 8), with 76.9% having received triple therapy (proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies). Notably, 23.1% had been treated with BCMA CAR-T therapy.

Safety Findings

• Adverse Events: All patients experienced treatment-related adverse events (TRAEs).

• Cytokine Release Syndrome (CRS): Occurred at grades 1 or 2 in all patients, with a median duration of 2.1 days.

• Grade ≥3 TRAEs: Predominantly haematological toxicities, such as lymphopenia (92.3%) and thrombocytopenia (61.5%).

• Other Observations: No instances of immune effector cell-associated neurotoxicity syndrome (ICANS) or TRAEs leading to treatment discontinuation or death.

Efficacy Findings

• Among 12 evaluable patients, the objective response rate (ORR) was an impressive 76.9%, as defined by the International Myeloma Working Group (IMWG) criteria.

• Complete Response (CR): 15.4% (2/13)

• Very Good Partial Response (VGPR): 23.1% (3/13)

• Partial Response (PR): 38.5% (5/13)

Future Directions

The promising safety and efficacy profile of QLS32015 underscores its potential as a novel therapeutic for RRMM patients. The dose-escalation phase continues, with DLT, MTD, and RP2D determinations forthcoming.