A Study to Evaluate the Efficacy and Safety of HLX15-IV Versus DARZALEX® in Combination with Lenalidomide-Dexamethasone (Rd) in Transplant-ineligible Patients with Newly Diagnosed Multiple Myeloma

A Randomized, Double-blind, Parallel-controlled, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of HLX15-IV Versus DARZALEX® in Combination with Lenalidomide-Dexamethasone (Rd) in Transplant-ineligible Patients with Newly Diagnosed Multiple Myeloma

This is a randomized, double-blind, parallel-controlled, multicenter, phase III study to compare the efficacy and safety of HLX15-IV in combination with Rd (HLX15-IV-Rd) versus DARZALEX® in combination with Rd (D-Rd) in patients with NDMM who are ineligible for autologous stem cell transplantation (ASCT).

Study Overview

• Status: Not yet recruiting
• Conditions: Newly Diagnosed Multiple Myeloma
• Intervention / Treatment: Drug: HLX15-IV; Drug: Darzalex

• Study Type: Interventional
• Enrollment (Estimated): 386
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Zhongshan hospital, Shanghai

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Capable to understand and sign the ICF.
2. Patients aged ≥ 18 years .
3. Patient must have documented multiple myeloma (MM) satisfying the International Myeloma Working Group (IMWG) diagnostic criteria for MM.
4. Newly diagnosed, untreated and not considered candidate for autologous stem cell transplantation (ASCT).
5. Patient must have an ECOG performance status score of 0.
6. Patient must have pretreatment clinical laboratory values.
7. Contraceptive use by men or women should be consistent with local regulations.
8. A WOCBP must have a negative serum pregnancy test at screening within 72 hours prior to randomization.

Exclusion Criteria:

1. Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
2. Patient has plasma cell leukemia or POEMS syndrome .
3. Patient has prior or current systemic therapy or ASCT for MM before randomization.
4. Patient has peripheral neuropathy or neuropathic pain Grade 2 or higher.
5. Patient has a history of malignancy (other than MM) within 3 years before randomization .
6. Patient has clinical signs of meningeal involvement of MM.
7. Patient has known COPD, persistent asthma, or a history of asthma within the last 2 years.
8. Patient is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have treponema pallidum antibodies (Anti-TP).
9. Patient is known to have active hepatitis B or C.
10. Patient has any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results.
11. Patient has clinically significant cardiac disease.
12. Patient has known allergies, hypersensitivity, or intolerance to treatment drugs.
13. Patient has history of drug abuse or substance abuse.
14. Patient is a woman who is pregnant, or breast-feeding, or planning to become pregnant or donate eggs (ova, oocytes).
15. Patient had radiation therapy within 14 days of randomization.
16. Patient had plasmapheresis within 28 days of randomization.
17. Patient had major surgery within 28 days before randomization.
18. Patient in clinical trials of any other drug or device within 3 months before randomization.
19. Patient has any condition could prevent, limit, or confound the protocol-specified assessments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX15-IV-Rd; HLX15-IV in combination with Lenalidomide-Dexamethasone (Rd)	Drug: HLX15-IV; recombinant anti-CD38 human monoclonal antibody injection
Active Comparator: DARZALEX-Rd; DARZALEX in combination with Lenalidomide-Dexamethasone (Rd)	Drug: Darzalex; recombinant anti-CD38 human monoclonal antibody injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IRC-assessed Week 24 rate of very good partial response (VGPR) or better	the percentage of patients achieving VGPR or CR (including sCR) until Week 24 after the date of randomization.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Week 24 rate of VGPR or better	the percentage of patients achieving VGPR or CR (including sCR) until Week 24 after the date of randomization	24 weeks
IRC- and investigator-assessed Week 12, 36 and 48 rate of VGPR or better	percentage of patients achieving VGPR or CR (including sCR) until Week 12, 36 and 48 after the date of randomization	12,36,48 weeks
IRC- and investigator-assessed partial response (PR) rate	the percentage of patients achieving PR at any time point after the date of randomization	48 weeks
IRC- and investigator-assessed complete response (CR) rate	the percentage of patients achieving CR at any time point after the date of randomization.	48 weeks
IRC- and investigator-assessed stringent complete response (sCR) rate	percentage of patients achieving sCR at any time point after the date of randomization	48 weeks
IRC- and investigator-assessed complete response (CR) or better rate	the percentage of patients achieving CR or sCR at any time point after the date of randomization.	48 weeks
IRC- and investigator-assessed overall response rate	the percentage of patients who achieve PR or better after the date of randomization.	48 weeks
IRC- and investigator-assessed time to response (TTR)	the time from the date of randomization to the date of initial documentation of a response (PR or better) for patient who had achieved a response of PR or better	48 weeks
IRC- and investigator-assessed duration of response (DOR)	the date of initial documentation of a response (PR or better) to either progressive disease according the IMWG criteria, or death, whichever occurs first	48 weeks
IRC- and investigator-assessed progression free survival (PFS)	the duration from the date of randomization to either progressive disease, according to the IMWG response criteria, or death, whichever occurs first.	48 weeks
Minimal residual disease (MRD) negative rate	the percentage of patients who achieve negative MRD at least once during the confirmed complete response (CR) or better according to the IMWG response criteria.	48 weeks
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (EORTC-QLQ-C30).	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (EORTC-QLQ-C30).Minimum and maximum values is according to the items, the score range of item 1-28 is 1-4, the score range of item 29-30 is 1-7. The higher the overall score is, the better the overall quality of life is.	48 weeks
EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire.	EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire.The description of health status is divided into five levels.Health Status Index range is -0.59-1.00, VAS range is 0-100.The higher the Health Status Index and VAS score are, the better the health condition is; the lower the dimension description score is, the fewer problems there are.	48 weeks
Incidence and severity of adverse events (AEs)	severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version [v] 5.0, vital signs and clinical laboratory test results	52 weeks
Time to reach maximum serum drug concentration at steady state (Tmax, ss)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	48 weeks
Time to reach maximum serum drug concentration(Tmax)	Detailed Outcome Measure will be defined in the Statistical Analysis Plan	48 weeks
Immunogenicity	Incidence of ADA and/or NAb for HLX15-IV and DARZALEX	48 weeks

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Estimated): March 26, 2025

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

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; Daratumumab
• Other Study ID Numbers: HLX15-IV-NDMM-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No