To Evaluate the Efficacy and Safety of QL2109 and DARZALEX FASPRO® in Multiple Myeloma

A Randomized, Multicenter, Double-Blind, Parallel-Controlled, Phase III Clinical Study to Evaluate QL2109/ DARZALEX FASPRO® in Combination With Pomalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor

This is a randomized, double-blind, multicenter trial，parallel control designed to evaluate treatment with pomalidomide + QL2109 + dexamethasone compared with pomalidomide + DARZALEX FASPRO® + dexamethasone in the participants with relapsed or refractory Multiple Myeloma.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: QL2109; Drug: Pomalidomide; Drug: Dexamethasone; Drug: DARZALEX FASPRO®

• Study Type: Interventional
• Enrollment (Estimated): 284
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: zhen cai, Professor; Phone Number: +086-0571-87236560; Email: caizhen1@sina.com
• Study Contact Backup: Name: baijun fang, Professor; Phone Number: +086-0371-65587418; Email: fdation@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females at least 18 years of age.
• Subject must have measurable disease of MM as defined by the criteria below:Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain multiple myeloma, for subjects without measurable disease in the serum or urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Subjects must have received prior antimyeloma treatment. The prior treatment must have included both a PI- and lenalidomide-containing regimens. Subjects who received only 1 line of prior treatment must have demonstrated PD on or within 60 days of completion of the lenalidomide containing regimen (ie, lenalidomide refractory).
• Subjects must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria on or after the last regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
• For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤Grade 1.

• Any of the following laboratory test results during Screening:

  1. Absolute neutrophil count ≥1.0 × 109/L;
  2. Hemoglobin level ≥75 g/L (≥4.65 mmol/L); (transfusions are not permitted to reach this level);
  3. Platelet count ≥75 × 109/L in subjects in whom <50% of bone marrow nucleated cells are plasma cells and platelet count ≥50 x 109/L in subjects in whom ≥50% of bone marrow nucleated cells are plasma cells;
  4. Alanine aminotransferase (ALT) level ≤2.5 times the upper limit of normal (ULN);Aspartate aminotransferase (AST) level ≤2.5 x ULN;
  5. Total bilirubin level ≤1.5 x ULN, (except for Gilbert Syndrome: direct bilirubin ≤1.5 × ULN);
  6. Creatinine clearance ≥30 mL/min
  7. Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤1.6 mmol/L).

Exclusion Criteria:

• Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
• History of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
• Clinical signs of meningeal involvement of MM.
• Previous therapy with any anti-CD38 monoclonal antibody.
• Previous exposure to pomalidomide.
• Subject has received antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before Cycle 1, Day 1 (C1D1).
• Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
• Subject has had major surgery within 2 weeks before randomization, or has not fully recovered from an earlier surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration.
• Ongoing ≥ Grade 2 peripheral neuropathy.
• Subject had ≥Grade 3 rash during prior therapy.
• Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pomalidomide Plus(+) QL2109 + Dexamethasone	Drug: QL2109; QL2109 will be given 1800 mg subcutaneously at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs.; Drug: Pomalidomide; Intervention Description：Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle; Drug: Dexamethasone; Dexamethasone will be administered at a dose of 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle
Active Comparator: Pomalidomide + DARZALEX FASPRO® + Dexamethasone	Drug: Pomalidomide; Intervention Description：Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle; Drug: Dexamethasone; Dexamethasone will be administered at a dose of 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle; Drug: DARZALEX FASPRO®; DARZALEX FASPRO® will be given 1800 mg subcutaneously at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Very Good Partial Response (VGPR) or Better	VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response[sCR]) according to the IMWG criteria during or after the study treatment.	from baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Very Good Partial Response (VGPR) or Better	VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response[sCR]) according to the IMWG criteria during or after the study treatment.	from baseline to week 12 and week 48
Overall Response Rate	Overall response rate is defined as the percentage of randomized subjects who achieve a best response of PR or better using modified IMWG criteria as their best overall response	from baseline to week 24 and week 48
Overall survival at 18 months	the probability of being alive 18 months after randomization	from baseline to 18 months

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Daratumumab
• Other Study ID Numbers: QL2109-301

Drug and device information, study documents

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