P-137: A phase 3, two-stage, randomized study of iberdomide maintenance versus lenalidomide maintenance post autologous stem cell transplantation in newly diagnosed multiple myeloma: EXCALIBER-Maintenance

Introduction: Trial in progress. For patients (pts) with newly diagnosed multiple myeloma (NDMM), maintenance with the immunomodulatory drug (IMiD®) lenalidomide (LEN) is the standard of care after autologous stem cell transplantation (ASCT). All pts remain at risk for relapse post ASCT, and pts may discontinue LEN maintenance due to adverse events; therefore, there is an unmet need for new drugs with improved activity and tolerability in the maintenance setting. Iberdomide (IBER) is a novel, potent oral cereblon E3 ligase modulator (CELMoD™) with increased tumoricidal activity and enhanced immune-modulatory effects compared with IMiD agents. The EXCALIBER-Maintenance phase 3 trial (NCT05827016) will compare the efficacy and safety of IBER maintenance with that of LEN maintenance post ASCT in pts with NDMM.

Methods: This randomized, multicenter, controlled, open-label study will be conducted in 2 stages: in Stage 1, ≈120 pts will be randomized 1:1:1:1 to 1 of 3 IBER doses or to the LEN arm to identify the optimal IBER dose as maintenance therapy after ASCT; in Stage 2, ≈1096 additional pts will be randomized 1:1 to receive the selected IBER dose or LEN, for efficacy and safety analyses (Stage 1 pts in the selected dose cohort and LEN arm will also be included). Pts will be stratified by minimal residual disease (MRD) status (negative vs positive [10-4 threshold]/indeterminate), cytogenetic risk profile (high vs standard/indeterminate) at study entry, and ISS staging at initial diagnosis (I–II vs III). Key eligibility criteria include age ≥18 years; 3–6 prior cycles of induction therapy (a proteasome inhibitor + an IMiD agent ± an anti-CD38 monoclonal antibody, or bortezomib + cyclophosphamide + dexamethasone) followed by a single or tandem ASCT with or without consolidation and has not relapsed following primary therapy or is considered not responsive. Treatment in the IBER arms will consist of 28-day (D) cycles (C) with IBER given orally on D1–21 at 0.75, 1.0, or 1.3 mg in Stage 1, or at the selected dose level in Stage 2. Treatment in the LEN arms will consist of 28-D cycles with oral LEN at 10 mg on D1–28. Treatment will continue until confirmed progressive disease (PD) or unacceptable toxicity. The primary efficacy endpoint will be progression-free survival (PFS), defined as time from randomization to PD or death, and the key secondary endpoints will be MRD negativity rate and overall survival (OS). The key secondary endpoints will be tested hierarchically after the primary endpoint demonstrates superiority. Other secondary endpoints include response improvement, PFS2, time to progression, time to next treatment, safety, and health-related quality of life. Interim analyses are planned for dose selection (Stage 1) and OS (Stage 2); PFS superiority may be analyzed when sufficient OS and PFS information is available to enable such an analysis. Enrollment is expected to begin in June 2023.

Results: N/A

Conclusions: N/A