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): daratumumab + lenalidomide approx 2 years. Subjects with a negative MRD (for at least 12 months) after 24 cycles of daratumumab-lenalidomide will discontinue daratumumab and continue with lenalidomide monotherapy until disease progression, or study cut-off date (whichever occurs first).
Subjects who did not achieve MRD negativity for at least 12 months after 24 cycles of daratumumab-lenalidomide will continue to receive daratumumab-lenalidomide until:
* MRD negativity for at least 12 months is reached. Subjects will then continue with lenalidomide monotherapy until disease progression, or study cut-off date (whichever occurs first). * Disease progression * Or study cut-off date (whichever occurs first).
* Arm D (experimental arm): elranatamab. Approx 2 years. Subjects with a negative MRD (for at least 12 months) after receiving M22 administration of elranatamab will discontinue study treatment with elranatamab.
Subjects who did not achieve MRD negativity for at least 12 months after M22 elranatamab administration will continue to receive elranatamab, every 24 weeks, until MRD negativity for at least 12 months is reached, disease progression, or study cut-off date (whichever occurs first).
Male or female subjects, aged over 18 but < 70 years old
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).
More than 1 focal lesion (≥5 mm diameter) on MRI.
Subjects previously treated with any systemic therapy for multiple myeloma. Patients are allowed corticosteroids before or during screening, as far as the total dose received is not >160 mg of dexamethasone (or equivalent) within 14 days before initiating induction therapy. Patients with concurrent radiotherapy within the 14 days before initiating induction therapy are not eligible (If possible, in these cases, enrolment should be deferred).
Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
Parallel
Elranatamab
DrugElranatamab is given to arm B patients in association with lenalidomide (for consolidation) and arm D patients in monotherapy (for maintenance) as experimental arms
Lenalidomide (Revlimid®)
DrugIn association with daratumumab, bortezomib and dexamethasone (Arm A), in association with elranatamab (Arm B), and in combination with daratumumab in maintenance (Arm C)
Daratumumab SC (Darzalex)
DrugDaratumumab is given in association with bortezomib, lenalidomide and dexamethasone in induction therapy (all patients) and consolidation arm A
Autologous Stem Cell Transplantation
Procedure/SurgeryASCT is performed in consolidation for Arm A patients after induction therapy with D-VRD
Bortezomib (Velcade®)
DrugBortezomib is given in associtaion with daratumumab, lenalidomide and dexamethasone in induction (all patients) and consolidation Arm A
Dexamethasone
DrugDexamethasone is given in association with daratumumab, bortezomib and lenalidomide in induction (all patients) and consolidation Arm A
Part 1 (induction/consolidation) from Randomization 1 (R1): to assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of Minimal Residual Disease (MRD) negativity rate
To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of MRD negativity rate.
Part 2 (maintenance) from Randomization 2 (R2): to assess whether maintenance therapy with elranatamab is superior to standard of care, in terms of Progression Free Survival (PFS).
To assess whether maintenance therapy with elranatamab is superior to standard of care, in terms of PFS.
Key secondary objectives: Part 1 (induction/consolidation) from R1: to assess whether consolidation therapy with elranatamab and lenalidomide is superior, in terms of PFS
To assess whether consolidation therapy with elranatamab and lenalidomide is superior, in terms of PFS
Key secondary objectives: Part I (induction/consolidation) from R1: to assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of Overal Survival (OS)
To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of OS
Part 1 (induction/consolidation) from R1: to assess the efficacy of consolidation therapy with elranatamab and lenalidomide compared to standard of care
To assess the efficacy of consolidation therapy with elranatamab and lenalidomide compared to standard of care: Overall response rate (ORR), Very good partial response (VGPR) rate, Complete response (CR) rate
Part 2 (maintenance) from R2: to assess the efficacy of maintenance therapy with elranatamab
To assess the efficacy of maintenance therapy with elranatamab: * Overall response rate (ORR) in maintenance * Very good partial response (VGPR) rate in maintenance * Complete response (CR) rate in maintenance
assess safety & Tolerability during induction, and during consolidation and maintenance therapy: Adverse events (AE), serious Adrverse events (SAE) and And adverse events of special interest (AESI) rates - Incidence of Treatment-Emergent Adverse Events
To assess safety during induction, and during consolidation and maintenance therapy: AEs, SAE and AESI rates , Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]
Throughout the study to evaluate the impact of treatment on health-related Quality of Life (QoL) using Rework questionnaire
To evaluate the impact of treatment on health-related QoL: Rework questionnaire
EXPLORATORY OBJECTIVES: to assess the impact of genomic markers (from Next generation sequencing (NGS) and Whole Genome Sequencing (WGS)) on outcome
To assess the impact of genomic markers (from NGS and WGS) on outcome: MRD negativity rate as determined by NGS with a sensitivity of at least 10-5 - PFS1 and OS
EXPLORATORY OBJECTIVES: to assess Immune mechanisms predicting Elra-Len vs ASCT efficacy
Impact of the microenvironment (Immune mechanisms predicting Elra-Len vs ASCT efficacy) according to outcome (MRD, PFS and OS) rates
EXPLORATORY OBJECTIVES: to assess the impact of PET imaging parameters/variables on outcome
rate of PET imaging positive / negative according to outcome (MRD, PFS and OS) rates
EXPLORATORY OBJECTIVES: To determine influence of M-component measurement assessed by mass spectrometry on outcome
To determine influence of M-component measurement assessed by mass spectrometry on outcome
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Intergroupe Francophone du Myelome
Lead sponsor
Pfizer
Collaborator
