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

Phase 3

Not yet recruiting

• Conditions: Newly Diagnosed Multiple Myeloma
• Interventions: Drug: HLX15-IV; Drug: Darzalex

• Registration Number: NCT06895512
• Lead Sponsor: Shanghai Henlius Biotech

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-10
• Study First Submitted QC: 2025-03-19
• Last Update Submitted: 2025-03-19
• Study First Posted: 2025-03-26
• Last Update Posted: 2025-03-26
• Study Start: 2025-04
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 386

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HLX15-IV-Rd	HLX15-IV	HLX15-IV in combination with Lenalidomide-Dexamethasone (Rd)
DARZALEX-Rd	Darzalex	DARZALEX in combination with Lenalidomide-Dexamethasone (Rd)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Time to reach maximum serum drug concentration at steady state (Tmax, ss)	48 weeks	Detailed Outcome Measure will be defined in the Statistical Analysis Plan
Investigator-assessed Week 24 rate of VGPR or better	24 weeks	the percentage of patients achieving VGPR or CR (including sCR) until Week 24 after the date of randomization
IRC- and investigator-assessed partial response (PR) rate	48 weeks	the percentage of patients achieving PR at any time point after the date of randomization
IRC- and investigator-assessed complete response (CR) or better rate	48 weeks	the percentage of patients achieving CR or sCR at any time point after the date of randomization.
IRC- and investigator-assessed time to response (TTR)	48 weeks	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
IRC- and investigator-assessed progression free survival (PFS)	48 weeks	the duration from the date of randomization to either progressive disease, according to the IMWG response criteria, or death, whichever occurs first.
IRC- and investigator-assessed Week 12, 36 and 48 rate of VGPR or better	12,36,48 weeks	percentage of patients achieving VGPR or CR (including sCR) until Week 12, 36 and 48 after the date of randomization
IRC- and investigator-assessed overall response rate	48 weeks	the percentage of patients who achieve PR or better after the date of randomization.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Health Status (EORTC-QLQ-C30).	48 weeks	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.
Time to reach maximum serum drug concentration(Tmax)	48 weeks	Detailed Outcome Measure will be defined in the Statistical Analysis Plan
IRC- and investigator-assessed complete response (CR) rate	48 weeks	the percentage of patients achieving CR at any time point after the date of randomization.
IRC- and investigator-assessed stringent complete response (sCR) rate	48 weeks	percentage of patients achieving sCR at any time point after the date of randomization
IRC- and investigator-assessed duration of response (DOR)	48 weeks	the date of initial documentation of a response (PR or better) to either progressive disease according the IMWG criteria, or death, whichever occurs first
Minimal residual disease (MRD) negative rate	48 weeks	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.
EuroQoL 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire.	48 weeks	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.
Immunogenicity	48 weeks	Incidence of ADA and/or NAb for HLX15-IV and DARZALEX
Incidence and severity of adverse events (AEs)	52 weeks	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

Trial Locations

Locations (1)

Zhongshan hospital, Shanghai; 🇨🇳 Shanghai, Shanghai, China