Preliminary results from a Phase Ia study of Qilu Pharmaceutical's novel anticancer drug, QLS32015, were presented at the 66th Annual Meeting of the American Society of Hematology (ASH) in San Diego. The study (NCT05920876) evaluated the safety and preliminary efficacy of QLS32015 in patients with relapsed/refractory multiple myeloma (RRMM). The findings suggest that QLS32015, a GPRC5D/CD3-targeting bispecific antibody, exhibits promising anti-tumor activity and is well-tolerated in this patient population.
QLS32015 is a humanized IgG1 T-cell retargeting bispecific antibody designed to simultaneously bind to GPRC5D, a G protein-coupled receptor highly expressed on multiple myeloma cells, and CD3, a component of the T-cell receptor complex. This dual targeting mechanism bridges T cells to tumor cells, facilitating T-cell-mediated destruction of cancer cells. Unlike conventional MHC/TCR pathways, QLS32015 creates an immune synapse, activating T cells to attack and kill tumor cells.
The open-label, dose-escalation/expansion Phase I trial enrolled patients with RRMM who had progressed on or were intolerant to existing treatments. Patients received QLS32015 monotherapy subcutaneously at doses ranging from 2 to 200 μg/kg, administered weekly or biweekly. The primary endpoints of the Phase Ia dose-escalation phase were to determine the dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D). The study utilized a combination of accelerated titration and Bayesian optimal interval strategies.
Patient Characteristics
As of August 31, 2024, a total of 13 patients were enrolled in the trial. The median age of participants was 61 years, with a median of 3 prior lines of therapy (range, 1 to 8). A significant proportion (76.9%) had received at least triple therapy, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. Furthermore, 23.1% of patients had prior exposure to B-cell maturation antigen (BCMA) CAR-T therapy, representing a heavily pre-treated population.
Safety and Tolerability
In terms of safety, one DLT was observed at the 54 μg/kg dose level; however, the MTD was not reached. Treatment-related adverse events (TRAEs) were reported in all patients. The most common TRAE was cytokine release syndrome (CRS), which was grade 1 or 2 in all patients, with a median duration of 2.1 days. The most common grade ≥3 TRAEs were hematological toxicities, including lymphopenia (92.3%) and thrombocytopenia (61.5%). Most non-hematological TRAEs were grade 1 or 2. Notably, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported, and there were no TRAEs leading to treatment discontinuation or death.
Efficacy
Efficacy data were available for 12 of the 13 enrolled patients. The objective response rate (ORR), assessed according to the International Myeloma Working Group (IMWG) criteria, was 76.9% (10/13). Among responders, two patients (15.4%) achieved complete response (CR), three (23.1%) achieved very good partial response (VGPR), and five (38.5%) achieved partial response (PR).
These preliminary findings suggest that QLS32015 demonstrates a tolerable safety profile and promising remission rates in patients with RRMM. The dose-escalation study is ongoing to determine the DLT, MTD, and RP2D.
