A Study in Participants With Relapsed or Refractory Multiple Myeloma for QLS4131

A Phase 3 Randomized Study Comparing QLS4131 Injection Versus Treatment Per Investigator's Choice in Participants With Relapsed or Refractory Multiple Myeloma

The purpose of this clinical trial is to evaluate the efficacy and safety of QLS4131 compared with the investigator's choice regimen (DPd or PVd) in participants with relapsed or refractory multiple myeloma (RRMM).

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: QLS4131; Drug: Pomalidomide Capsules; Drug: Bortezomib for Injection; Drug: Daratumumab Injection (Subcutaneous Injection); Drug: Dexamethasone

Detailed Description

This study is an open, multicenter, randomized controlled phase III clinical trial aimed at evaluating the efficacy and safety of QLS4131 compared to the investigator's choice regimen (DPd or PVd) in participants with relapsed or refractory multiple myeloma who have previously received 1-4 lines of therapy and have been exposed to three classes of drugs (proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies). The plan is to enroll approximately 300 participants, who will be randomly assigned to the experimental group and the control group in a 1:1 ratio. Approximately 150 participants in the experimental group will receive QLS4131 treatment, while about 150 participants in the control group will receive the investigator's choice of treatment (DPd or PVd).

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: LUGUI QIU, Doctor of Medicine (MD); Phone Number: 022-23608124; Email: qiulg@ihcams.ac.cn
• Study Contact Backup: Name: GANG AN, Doctor of Medicine (MD); Phone Number: 13502181109; Email: angang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years.
• Documented initial diagnosis of multiple myeloma according to IMWG diagnostic criteria.
• At least one of the following measurable disease indicators:
• Serum M-protein ≥ 5 g/L
• Urine M-protein ≥200 mg/24h
• Serum free light chain (FLC) test: affected FLC level ≥100 mg/L and abnormal serum FLC ratio.
• Received 1-4 prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).
• Willing and able to comply with the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Prior treatment with both the BCMA-targeted therapy and the GPRC5D-targeted therapy. Patients who have received either BCMA-targeted or GPRC5D-targeted therapy alone are eligible.
• Known hypersensitivity to any of the ingredients of investigational drug.
• Diagnosis of plasma cell leukemia(peripheral blood plasma cells ≥5%),or primary light chain amyloidosis.
• Known active central nervous system (CNS) involvement, or clinical signs and symptoms suggestive of meningeal involvement by multiple myeloma.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QLS4131; Participants will receive QLS4131 injection until death, disease progression, initiation of new anti-tumor therapy, withdrawal of informed consent to participate in the study, or other reasons for discontinuation of study treatment, whichever occurs first.	Drug: QLS4131; QLS4131 will be administered subcutaneously.
Active Comparator: The investigator's choice regimen (DPd or PVd ); Participants will receive DPd or PVd until death, disease progression, initiation of new anti-tumor therapy, withdrawal of informed consent to participate in the study, or other reasons for discontinuation of study treatment, whichever occurs first.	Drug: Pomalidomide Capsules; The DPd treatment regimen, one cycle every 28 days: Pomalidomide 4mg/d orally, on days 1-21;The PVd treatment regimen, one cycle every 21 days: Pomalidomide 4 mg/d orally, on days 1-14 of each treatment cycle.; Drug: Bortezomib for Injection; The PVd treatment regimen, with one cycle every 21 days: Bortezomib on days 1, 4, 8, and 11 of cycles 1-8, and on days 1 and 8 from cycle 9 onwards.; Drug: Daratumumab Injection (Subcutaneous Injection); The DPd treatment regimen, one cycle every 28 days: on days 1, 8, 15, and 22 of cycles 1 and 2; on days 1 and 15 from cycles 3-6; and on day 1 from cycle 7 onwards.; Drug: Dexamethasone; The DPd treatment regimen, one cycle every 28 days: Dexamethasone 20 mg orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 (total 40 mg per week). The PVd treatment regimen, one cycle every 21 days: Dexamethasone 20 mg orally, on days 1, 2, 4, 5, 8, 9, 11, and 12 of cycles 1-8, and on days 1, 2, 8, and 9 from cycle 9 onwards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by independent review committee	PFS is defined as the duration from the date of randomization to either PD or death, whichever comes first. Disease progression will be determined according to the IMWG 2016 response criteria.	up to 2 years after the last enrolled participant receives the first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by investigator	PFS is defined as the duration from the date of randomization to either PD or death, whichever comes first. Disease progression will be determined according to the IMWG 2016 response criteria.	up to 2 years after the last enrolled participant receives the first dose of study drug
Very good partial response or better rate	Very good partial response or better rate is defined as the percentage of participants who achieve very good partial response or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 response criteria.	up to 2 years after the last enrolled participant receives the first dose of study drug
Negativity rate of minimal residual disease (MRD)	Defined as the proportion of participants achieving MRD-negative status.	up to 2 years after the last enrolled participant receives the first dose of study drug
Sustained MRD negativity rate	Defined as the proportion of participants achieving MRD-negative status and maintaining it for at least 1 year.	up to 2 years after the last enrolled participant receives the first dose of study drug
6-month MRD negativity rate	The proportion of participants achieving a response of CR or better and MRD-negative status at 6 months post-randomization.	up to 2 years after the last enrolled participant receives the first dose of study drug
12-month MRD negativity rate	The proportion of participants achieving a response of CR or better and MRD-negative status at 12 months post-randomization.	up to 2 years after the last enrolled participant receives the first dose of study drug
Objective response rate	Objective response rate is defined as the percentage of participants who achieve PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 response criteria.	up to 2 years after the last enrolled participant receives the first dose of study drug
Complete response or better rate	Complete response or better rate is defined as the percentage of participants who achieve CR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 response criteria.	up to 2 years after the last enrolled participant receives the first dose of study drug
Duration of response	DoR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG 2016 response criteria or death from any cause.	up to 2 years after the last enrolled participant receives the first dose of study drug
PFS Rate at 6, 12, and 18 Months	Percentage of participants who remain alive and progression-free at 6, 12, and 18 months after randomization, as assessed by both the independent review committee (IRC) and the investigator according to IMWG 2016 response criteria.	6, 12, and 18 months after randomization
Overall survival	OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.	up to 2 years after the last enrolled participant receives the first dose of study drug
OS Rate at 12 and 24 Months	Percentage of participants who remain alive at 12 and 24 months after randomization.	12 and 24 months after randomization
Number of Participants with Treatment-Emergent Adverse events (TEAE) by Severity	Number of participants with AEs by Severity will be reported.	up to 2 years after the last enrolled participant receives the first dose of study drug
Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)	Change from baseline scores	up to 2 years after the last enrolled participant receives the first dose of study drug

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2026
• Primary Completion (Estimated): December 14, 2029
• Study Completion (Estimated): May 21, 2030

Study Registration Dates

• First Submitted: November 6, 2026
• First Submitted That Met QC Criteria: November 6, 2026
• First Posted (Actual): November 12, 2026

Study Record Updates

• Last Update Posted (Actual): November 12, 2026
• Last Update Submitted That Met QC Criteria: November 6, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Drug Administration Routes; Drug Therapy; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Dexamethasone; Injections; pomalidomide; daratumumab; Injections, Subcutaneous
• Other Study ID Numbers: QLS4131-301

Drug and device information, study documents

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