QLS4131 Combination Therapy in Malignant Plasma Cell Neoplasms

A Multicenter, Open-Label Phase II Study to Evaluate QLS4131 Combination Therapy in the Treatment of Malignant Plasma Cell Neoplasms

The purpose of the study is to compare the efficacy of QLS4131(SC) in combination with QL2109, with or without pomalidomide or lenalidomide, and QLS4131 (SC) in combination with QL2109, and QLS4131 (SC) in combination with Pomalidomide, and QLS4131(SC) in combination with QL2109 and Lenalidomide.

Study Overview

• Status: Not yet recruiting
• Conditions: Malignant Plasma Cell Neoplasms
• Intervention / Treatment: Drug: Dexamethasone; Drug: QLS4131; Drug: QL2109; Drug: Pomalidomide; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YU HU, Doctor of Medicine (MD); Phone Number: 027-85726387; Email: dr_huyu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Diagnosis of multiple myeloma confirmed according to the 2016 International Myeloma Working Group (IMWG) diagnostic criteria, or diagnosis of plasma cell leukemia and primary light-chain amyloidosis confirmed in accordance with relevant guidelines.;

For patients with multiple myeloma and plasma cell leukemia, measurable disease at screening is defined as meeting any one of the following:

• Serum M-protein ≥0.5 g/dL (5 g/L);
• Urine M-protein ≥200 mg/24 hours;
• Serum immunoglobulin free light chain ≥10 mg/dL (100 mg/L) with an abnormal serum immunoglobulin κ/λ free light chain ratio.

For patients with light-chain amyloidosis:Measurable disease is defined as Involved serum free light chain ≥ 50 mg/L with an abnormal light chain ratio,ordifference between involved and uninvolved serum free light chains (dFLC) ≥ 50 mg/L.

Exclusion Criteria:

• History of Grade 3 or higher cytokine release syndrome (CRS) associated with any T-cell redirecting therapy (e.g., CD3-redirecting technologies or CAR-T cell therapy);

• Patients who received any of the following prior anti-tumor therapies before the first dose of investigational productt:

  1. Previous treatment with BCMA/GPRC5D/CD3-targeted therapy;

  2. Received any anti-tumor therapy within 4 weeks prior to the first dose, except for the following circumstances:

     • Cytotoxic therapy or small-molecule targeted therapy within 2 weeks or 5 half-lives, If the half-life is unknown, the washout period shall be 2 weeks (whichever is longer);
     • Immunomodulatory drug therapy within 7 days
     • Genetically modified adoptive cell therapy within 3 months.;
     • Traditional Chinese medicine with anti-tumor indications within 14 days.;
     • Radiotherapy within 14 days
• Prior intolerance to Pomalidomide (applies to treatment cohorts containing Pomalidomide);
• Prior intolerance to Lenalidomide (applies to treatment cohorts containing Lenalidomide);
• Prior intolerance to QL2109 (applies to treatment cohorts containing QL2109).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QLS4131(SC) in combination with QL2109, with or without Pomalidomide or Lenalidomide; Participants will receive QLS4131 and QL2109 as SC injections; Pomalidomide/ Lenalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.	Drug: Dexamethasone; Dexamethasone will be administered orally or intravenously.; Drug: QLS4131; QLS4131 will be administered subcutaneously.; Drug: QL2109; QL2109 will be administered subcutaneously.; Drug: Pomalidomide; Pomalidomide will be self-administered as a single dose orally.; Drug: Lenalidomide; Lenalidomide will be self-administered as a single dose orally.
Experimental: QLS4131(SC) in combination with QL2109; Participants will receive QLS4131 and QL2109 as SC injections; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.	Drug: Dexamethasone; Dexamethasone will be administered orally or intravenously.; Drug: QLS4131; QLS4131 will be administered subcutaneously.; Drug: QL2109; QL2109 will be administered subcutaneously.
Experimental: QLS4131(SC) in combination with Pomalidomide; Participants will receive QLS4131 as SC injections; Pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.	Drug: Dexamethasone; Dexamethasone will be administered orally or intravenously.; Drug: QLS4131; QLS4131 will be administered subcutaneously.; Drug: Pomalidomide; Pomalidomide will be self-administered as a single dose orally.
Experimental: QLS4131(SC) in combination with QL2109 for injection and Lenalidomide; Participants will receive QLS4131 and QL2109 as SC injections; Lenalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.	Drug: Dexamethasone; Dexamethasone will be administered orally or intravenously.; Drug: QLS4131; QLS4131 will be administered subcutaneously.; Drug: QL2109; QL2109 will be administered subcutaneously.; Drug: Lenalidomide; Lenalidomide will be self-administered as a single dose orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	To evaluate the tolerability and safety of subcutaneous administration of QLS4131 for Injection in combination with other agents in patients with malignant plasma cell neoplasms	From time of the first dose of QLS4131 to end of DLT period (28 days)
MTD	To determine the maximum tolerated dose (MTD)	Up to 2 years
ORR (Partial Response [PR] or Better)	Overall response (PR or better) is defined as percentage of participants who have a PR or better per International Myeloma Working Group (IMWG) criteria.	Up to 2 years
Overall Minimal Residual Disease (MRD)	MRD-negative is defined as proportion of participants who achieve MRD negativity at a threshold of 10^-5 at any timepoint after the first dose of study drug and before disease progression or start of subsequent antimyeloma therapy.	Up to 2 years

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Dexamethasone; pomalidomide
• Other Study ID Numbers: QLS4131-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No