A Phase 3, Open-label, Controlled, Randomized Study of Newly Diagnosed Multiple Myeloma Treatment, Designed to Evaluate the Efficacy and Safety of the Elranatamab-lenalidomide Combination as a Replacement for Chemotherapy Followed by Autologous Stem Cell Transplant in the Consolidation Phase, and to Compare Elranatamab With Standard of Care in the Maintenance Phase
This study is designed as a multicenter, randomized, parallel groups, open-label, phase 3 study in subjects with untreated newly diagnoses Multiple Myeloma eligible for ASCT. 824 patients will be enrolled in this study from approximately 70 study sites. The 2 parts in the Treatment Phase are described below. Part 1: Induction/ASCT/Consolidation Phase (1:1 Randomization) After the screening period, patients will be randomly allocated (1:1) to either: * Arm A (standard of care arm): standard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, D-VRd consolidation therapy * Arm B (experimental arm): standard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy. Part 2: Maintenance Phase (1:1 Re-randomization) Patients will be re-randomized (1:1) and will enter the Maintenance Phase upon completion of consolidation therapy. * Arm C (standard of care arm): lenalidomide * Arm D (experimental arm): elranatamab
• Male or female subjects, aged over 18.
• Patients have provided voluntary written informed consent before performing any study-related procedure.
• Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
• Patients with documented symptomatic NDMM according to CRAB and/or SLIM criteria, with measurable disease as defined by:
‣ Presence of ≥10% monoclonal plasma cells in the bone marrow OR presence of a biopsy-proven plasmacytoma. In addition, the patient must have ≥1 of the following myeloma defining events:
‣ \- Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than upper limits of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL).
‣ \- Renal insufficiency: creatinine clearance \< 40mL/min/1.73 m2 using CKD-EPI or serum creatinine \>177 μmol/L (\>2 mg/dL).
‣ \- Anemia: hemoglobin \>2 g/dL below the lower limit of normal (LLN) or hemoglobin \<10 g/dL.
∙ Bone lesions: ≥1 osteolytic lesion on skeletal radiography, CT or PET-CT.
∙ Clonal bone marrow plasma cell percentage ≥60%.
∙ Serum involved/uninvolved free light chain ratio ≥100.
∙ More than 1 focal lesion (≥5 mm diameter) on MRI.
⁃ Measurable disease as defined by serum M-component ≥5 g/L, and/or urine M-component ≥200 mg/24 h and/or serum FLC ≥100 mg/L.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
• Patients must have clinical laboratory values (within 15 days of initiating induction therapy) as follows:
• • Hemoglobin ≥7.5 g/dL (≥5 mmol/L). Prior red blood cell (RBC) transfusion or the use of recombinant human erythropoietin is permitted.
• • Absolute neutrophil count (ANC) ≥1.0 G/L (granulocyte colony stimulating factor \[G-CSF\] use is permitted).
• • Aspartate aminotransferase (AST) ≤3 x ULN.
• • Alanine aminotransferase (ALT) ≤ 3 x ULN.
• • Total bilirubin ≤3 x ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, that require a direct bilirubin ≤3 x ULN).
• • Calculated creatinine clearance ≥40 mL/min/1.73 m².
• • Albumin corrected serum calcium ≤14 mg/dL (\<3.5 mmol/L); or free-ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L).
• • Platelet count ≥50 Giga/L for subjects who have \<50% of bone marrow nucleated cells as plasma cells. If not, platelet count \>30 G/L (platelets transfusions done during the 15 days before initiating induction therapy are not permitted).
• Women of childbearing potential must have a negative serum or urine pregnancy test during the screening period before randomization AND within 3 days before of initiating induction therapy.