Clinical Research Directory

A Study to Compare the Efficacy and Safety of BMS-986393 Versus Standard Regimens in Adult Participants With Relapsed or Refractory and Lenalidomide-exposed Multiple Myeloma (QUINTESSENTIAL-2)

The purpose of this study is to compare the efficacy and safety of arlo-cel (BMS-986393) versus standard regimens in adult participants with Relapsed or Refractory and Lenalidomide-exposed Multiple Myeloma.

A Phase 2, Single Arm Multicenter, Study Testing Mezigdomide, Carfilzomib, and Dexamethasone (480Kd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM)

Despite advances in multiple myeloma (MM) therapy, patients continue to suffer from frequent relapses and treatment-resistant disease. Therefore, additional novel, safe, and effective therapies are needed to drive deeper and more prolonged responses for patients with RRMM. Mezigdomide (also known as CC-92480 or BMS-986348) is a novel, highly potent cereblon (CRBN)-E3 ligase modulating drug (CELMoD) and represents a new generation of CRBN-modulating (CM) agents optimized to induce rapid and robust degradation of the transcription factors Aiolos and Ikaros, which are important regulators for lymphocyte development and differentiation. CC-92480 was discovered via characterization of structure-activity relationships and exhibits enhanced autonomous cell killing activity in MM cells compared to lenalidomide and pomalidomide due to its increased efficiency at inducing Aiolos and Ikaros degradation. The increased potency of Mezigdomide (also overcomes lenalidomide and pomalidomide resistance in preclinical models inducing potent antiproliferative activity and apoptosis in MM cells with acquired resistance to lenalidomide or pomalidomide. Carfilzomib is a selective PI that irreversibly binds the proteasome, eliciting antimyeloma activity through unfolded protein stress response and other mechanisms. Carfilzomib is indicated for the treatment of RRMM in combination with dexamethasone (Kd), lenalidomide plus dexamethasone (KRd), and with anti-CD38 monoclonal antibodies daratumumab and isatuximab plus dexamethasone (DKd and IsaKd). However, as lenalidomide has become the foundation for a wide range of regimens used in newly diagnosed multiple myeloma (NDMM) and early in the therapeutic course of MM, KRd is not always a relevant therapeutic option in RRMM. In addition, given the increasing use of anti-CD38 mAb therapy in NDMM and early lines of therapy, DKd and IsaKd will also become less attractive therapeutic options in RRMM. This study will explore mezigdomide with carfilzomib and dexamethasone (480Kd) in a patient population where KRd and DKd/IsaKd are not appropriate treatment options due to prior treatment with lenalidomide and anti-CD38 mAb therapy. Mezigdomide has shown marked synergy in combination with PIs in lenalidomide resistant mouse xenograft models with combination treatment resulting in near complete tumor regressions. The combination of mezigdomide with carfilzomib has also shown synergistic anti-proliferative activity in MM cell lines resistant to lenalidomide and deeper tumor cell killing than combinations of other CELMoD agents with carfilzomib. These preclinical data demonstrate the potent synergy of mezigdomide with PIs, including carfilzomib, and the ability of mezigdomide to overcome IMiD drug resistance. The pleiotropic anti-myeloma effects of mezigdomide include its potent tumoricidal activity in IMiD (lenalidomide and pomalidomide)-resistant cell lines, synergistic anti-tumor effects when combined with proteasome inhibitors and dexamethasone, and the promising clinical activity seen in the Phase 1/2 CC-92480-MM-002 study, all make 480Kd a highly attractive regimen to be further investigated for the treatment of RRMM patients. This study is a single arm multicenter, Phase 2 study investigating the efficacy and safety of 480Kd in participants with RRMM who received at least 1 prior line of therapy, including lenalidomide and an anti-CD38 mAb, however are carfilzomib naïve.

Dual-target BCMA-CD19 CAR-T Cell Therapy for RR/MM With Extramedullary Infiltration

This is a multicenter, open-label, non-randomized, single-arm clinical trial. Patients with relapsed/refractory multiple myeloma accompanied by extramedullary infiltration will receive BCMA - CD19 CAR-T cell therapy. The primary objective is to prospectively evaluate the safety of dual-targeting BCMA and CD19 CAR - T cell therapy for extramedullary infiltration in relapsed/refractory multiple myeloma. The primary endpoints are to assess the type and incidence of dose-limiting toxicity (DLT) within one month after the infusion of BCMA-CD19 CAR-T cells in patients, as well as the incidence and severity of adverse events within one month after the infusion. It is expected that no more than 18 participants will be recruited.

Dual-target BCMA-GPRC5D CAR-T Cell Therapy for RR/MM With Extramedullary Infiltration

This is a multicenter, open-label, non-randomized, single-arm clinical trial. Patients with relapsed/refractory multiple myeloma accompanied by extramedullary infiltration will receive BCMA - GPRC5D CAR-T cell therapy. The primary objective is to prospectively evaluate the safety of dual-targeting BCMA and GPRC5D CAR - T cell therapy for extramedullary infiltration in relapsed/refractory multiple myeloma. The primary endpoints are to assess the type and incidence of dose-limiting toxicity (DLT) within one month after the reinfusion of BCMA-GPRC5D CAR-T cells in patients, as well as the incidence and severity of adverse events within one month after the reinfusion. It is expected that no more than 18 participants will be recruited.

Intravenous Autologous CD19 CAR-T Cells for R/ R MM, B-ALL, and B-Cell Lymphoma

This is an open label, single-site, dose-escalation study in up to 18 participants with Relapsed or Refractory Multiple Myeloma, Acute B-Cell Leukemia, and B-Cell Lymphoma. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART

Purinostat Mesylate Combined With Pomalidomide Capsules and Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Primary Purpose Phase Ib. To determine the Maximum Tolerated Dose (MTD) and establish the Recommended Phase IIa Dose (RP2D) of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed or refractory multiple myeloma. Phase IIa. To further evaluate the safety and tolerability of Purinostat Mesylate for Injection at the RP2D combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM). Secondary Objectives Phase Ib 1. To evaluate the safety and tolerability of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in the treatment of relapsed or refractory multiple myeloma. 2. To assess the pharmacokinetic (PK) parameters of the combination therapy in patients with relapsed or refractory multiple myeloma. 3. To observe the preliminary efficacy of the combination therapy in patients with relapsed or refractory multiple myeloma. Phase IIa 1. To evaluate the preliminary efficacy of the combination therapy in patients with relapsed and refractory multiple myeloma (RRMM). 2. To characterize the population pharmacokinetic (PPK) profile of the combination therapy in patients with relapsed or refractory multiple myeloma (RRMM).