A Study of GR1803 Injection Versus Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Participants With Relapsed or Refractory Multiple Myeloma

Official title

A Phase 3, Multicenter, Open-Label, Randomized Study Comparing GR1803 Injection Versus Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy Including Lenalidomide and Proteasome Inhibitors

Overview

The purpose of this study is to compare the efficacy of GR1803 Injection with daratumumab in combination with pomalidomide and dexamethasone (DPd).

Interventions

• Drug GR1803 injection
  Participants received intravenous GR1803 injection at a dose of 180 ug per kilogram, which had been preceded by step-up doses of 10 and 30 ug per kilogram.
• Drug Daratumumab
  Participants received subcutaneous Daratumumab at a dose of 1800 mg.
• Drug Pomalidomide
  Participants received Pomalidomide at a dose of 4 mg on days 1 to 21 of each cycle (28 days).
• Drug Dexamethasone
  Participants received once-weekly dexamethasone at a dose of 40 mg (≤75 years) or 20 mg (\>75 years).

Primary outcome measures

• Progression Free Survival (PFS) [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Overall Survival (OS) [Time frame: Up to 5 years]
• Progression Free Survival on Next-line Therapy (PFS2) [Time frame: Up to 5 years]
• Overall Response (Partial Response [PR] or Better) [Time frame: Up to 5 years]
• Complete Response (CR) or Better [Time frame: Up to 5 years]
• Duration of Response [Time frame: Up to 5 years]
• Duration of Complete Response [Time frame: Up to 5 years]
• Time to Response [Time frame: Up to 5 years]
• Minimal Residual Disease (MRD)-negativity [Time frame: Up to 5 years]
• Number of Participants with Adverse Events (AEs) by Severity [Time frame: Up to 5 years]
• Serum Concentration of GR1803 Injection [Time frame: Up to 5 years]
• Number of Participants with Anti-drug Antibodies (ADAs) to GR1803 Injection [Time frame: Up to 5 years]
• Change from Baseline in Overall Health-related Quality of Life as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Have an eastern cooperative oncology group (ECOG) performance status score of 0, 1, or 2 at screening and baseline.
• Diagnosed as multiple myeloma according to the diagnostic criteria of the International Myeloma Working Group (IMWG) diagnostic criteria.
• Received 1 to 3 prior line(s) of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide; a. participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
• Documented evidence of progressive or stable disease based on investigator's determination of response by IMWG criteria on or after their last regimen.
• Measurable disease at screening and baseline as defined by any of the following: 1) serum M-protein level greater than or equal to (>=) 5 gram per liter (g/L); or 2) urine M-protein level >=200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain >=100 mg/L and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Have clinical laboratory values within the specified range.
• Have an understanding of and comply with the clinical trial protocol requirements, voluntarily participate in the clinical trial, and sign the informed consent form.

Exclusion criteria

• Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or amyloidosis (including primary and secondary).
• History or clinical signs of central nervous system involvement or meningeal involvement of multiple myeloma .
• Received any prior B cell maturation antigen (BCMA)-directed therapy.
• Has disease that is considered refractory or intolerant to an anti-cluster of differentiation 38 (CD38) targeted therapy or Pomalidomide.
• Prior antitumor therapy, within 21 days (PI 、IMiDs or radiotherapy within 14 days, clinical trial vaccine within 28 days, Gene modified adoptive cell therapy within 3 months, allogeneic stem cell transplantation within 6 months, autologous stem cell transplantation within 12 weeks) prior to first dose of study drug.
• Received a cumulative dose of corticosteroids equivalent to >=140 mg of prednisone within 14 days prior to first dose of study drug.
• Grade >= 2 peripheral neuropathy at screening.
• History of Guillain Barre Syndrome (GBS) or variant GBS.
• The following medical conditions: active infecion, human immunodeficiency virus (HIV) infection, hepatitis B or C infection, Syphilis infection, thromboembolic events or cerebrovascular events less than or equal to (<=) 6 m, seizure attacks less than or equal to (<=) 6 m.
• Active malignancies other than relapsed/refractory multiple myeloma within 3 years prior to screening.
• Active autoimmune disease or history of autoimmune disease.
• Received a live, attenuated vaccine within 4 weeks before first dose of study drug.
• Have major surgery within 2 weeks before first dose of study drug.
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients.
• Pregnant, lactating female.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences — Tianjin

Identifiers

NCT: NCT07452198 · GR1803-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗