Qilu Pharma Unveils First-in-Human Clinical Data of QLS4131, a Novel GPRC5D×BCMA×CD3 Trispecific Antibody, in Relapsed/Refractory Multiple Myeloma at ASH 2025

2025 American Society of Hematology（ASH）The annual meeting will be held in Orlando, Florida, USA from December 6 to December 9 local time, and the regular abstracts have been published.

Qilu Pharmaceutical Co., Ltd. willNext-Generation Product Unveiled for the First Time at This ConferenceGPRC5D×BCMA×CD3 Three Antibodies QLS4131InRelapsed or Refractory Multiple Myeloma（RRMM）Among patientsFirst-in-Human TrialPreliminary research results.

Screenshot source: ASH official website

QLS4131 is a BCMA/GPRC5D/CD3 trispecific antibody. Preclinical data show that, compared to the reference product, QLS4131 exhibits higher affinity for multiple myeloma cell lines and can effectively eliminate dual targets.(BCMA and GPRC5D)And single-target(BCMA or GPRC5D)Tumor cells expressing the target, their tumor cell killing activity is significantly higher than that of the reference product.

This is an evaluationA Phase I Clinical Study of QLS4131 in RRMM Patients: Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy（NCT06500507）。

During the "dose escalation phase," Qilu Pharmaceutical recruited patients with measurable RRMM whose disease had progressed after existing treatments or who could not tolerate the current treatments. The dose escalation included:

• Intravenous Injection（IV）The dose starts from 0.06µg/kg Increase to 30µg/kg, once a week（QW）Administration;

• Subcutaneous Injection（SC）Dose from 30µg/kg Increase to 600µg/kg, once every two weeks（Q2W）Administration.

The patient at the first target dose(From 3µg/kg Dose Level Start)Previously received 1 or 2 incremental doses（SUD）`, to alleviate cytokine release syndrome`（CRS）。

As of July 15, 2025, a total of 17 patients have received QLS4131 treatment, with doses ranging from 0.06 to 30.µg/kg（IV，QW）. In addition, another 3 patients in the group received 30µg/kg QLS4131 Treatment（SC，Q2W）。

The median age of the patients was 59 years, and the median number of prior treatment lines was 3. Among them, 64.7% of the patients had received 3 or more lines of treatment, and 35% of the patients had undergone stem cell transplantation.

The results showed that in ≥1µg/kg A response was observed in the dose group. In15 namesAcceptQLS4131 Intravenous InjectionAmong patients who have been treated and meet the response evaluation criteria,ORR is 60%（≥VGPR 40%）。In 30µg/kg In the dose group,100% of patients achieved VGPR or better relief.。

In addition, at 10µg/kg Intravenous InjectionIn the dose group, there isTwo patients had previously failed BCMA-targeted CAR-T/CAR-NK therapy, and currently, one of them...One case achieved strict complete remission. (SCR)，Another case achieved partial remission. (PR)。

In terms of safety, QLS4131 demonstrated generally manageable tolerability. No dose-limiting toxicity was observed.（DLT）, and has not reached the maximum tolerated dose（MTD）. The most common treatment-related adverse events（TRAE）For cytopenia and CRS, the overall incidence rate of CRS was 80%. No immune effector cell-associated neurotoxicity syndrome occurred.（ICANS）。

The researchers concluded that,QLS4131 The toxicity was tolerable, no DLT was observed, andCompared with competitors(such as Johnson & Johnson's JNJ-79635322)Compared with the published data, the incidence of GPRC5D-related adverse reactions was lower.The main efficacy data showed that positive responses were observed even at low dose levels. The trial is still ongoing, and the MTD, RP2D, and DLT remain to be determined.

Insight database shows that globally under research and developmentGPRC5D×BCMA×CD3 Trispecific Antibody: 13 Versions, 6 of Which Have Entered Clinical Stages, Respectively FromTian Guangshi（MBS314）、Innovent（IBI3003）、Qilu（QLS4131）、Simcere Pharma/AbbVie（SIM0500）、Johnson & Johnson（JNJ-79635322）。

Screenshot source: Insight database