ONGOING CLINICAL TRIALS IN MULTIPLE MYELOMA

Abstract

a) BCMA-Targeted Therapies:I. CAR-T Cell Therapies: 1- KarMMa-3 Trial: This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of ide-cel versus standard regimens in subjects with R/R multiple myeloma. Ide-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens. 2- CARTITUDE-4 Trial: The purpose of this study is to compare the efficacy of ciltacabtagene autoleucel (cilta-cel) with standard therapy, either PVd or DPd. A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients.II. Bispesific Antibodies: 1- MajesTEC-1 Trial: The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose. Teclistamab resulted in a high rate of deep and durable response in patients with triple-class–exposed relapsed or refractory multiple myeloma. 2- MagnetisMM-3 Trial: The purpose of the study is to evaluate whether single-agent Elranatamab can provide clinical benefit in participants with R/R multiple myeloma. Elranatamab induced deep and durable responses with a manageable safety profile.III. Drug-Antibody Conjugates: 1- DREAMM-7 Trial: This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B). BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had R/R multiple myeloma after at least one line of therapy.b) Selinexor Combinations: 1- Updated Results Of Boston Trial By Prior Therapies: Stratified subgroup data from longer follow-up in the BOSTON trial confirm the PFS benefit of SVd over Vd in patients. 2- STOMP Trial: This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with R/R multiple myeloma and newly diagnosed multiple myeloma. X‐containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survivalc) Venetoclax Combinations: 1- CANOVA Trial: A study designed tocompare progression-free survival (PFS) in participants with t(11;14)-positive MM treated with venetoclax in combination with dexamethasone versus pomalidomide in combination with dexamethasone. Patients with BCL2high or gain(1q) had numerically improved clinical efficacy with VenDex versus PomDex.d) CELMoDs (Cereblon E3 Ligase Modulation Drugs):1- CC-92480-MM-001 Trial: This is an open-label, multi-center, international, Phase 1/2 study to assess the safety, PK and efficacy of mezigdomide monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM). The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects.2- CC-220-MM-001 Trial: This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study. Iberdomide plus dexamethasone was generally safe and showed meaningful clinical activity in heavily pretreated patients with multiple myeloma, including in disease that was refractory to immunomodulatory drugs.