Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S496 NJ, USA. 18Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland Context: Mezigdomide (MEZI) is a novel, potent oral cereblon E3 ligase modulator (CELMoD™) with enhanced antimyeloma effects compared with immunomodulatory drugs (IMiDs®). Preclinically, MEZI has shown potent synergy with dexamethasone and bortezomib, and preliminary Phase I/II trial results showed encouraging efficacy and safety of MeziVd in RRMM. The SUCCESSOR-1 trial (NCT05519085) will compare head-to-head the efficacy and safety of MEZI versus pomalidomide in RRMM. Methods: This multicenter, open-label, Phase III trial comprises 2 stages. In Stage 1, 140 patients will be randomized 1:1:1:1 to 1.0, 0.6, or 0.3 mg MEZI plus Vd or PVd to select the optimal MEZI dose based on efficacy, safety, pharmacokinetic, pharmacodynamic, and exposure–response analyses. In Stage 2, 620 additional patients will be randomized 1:1 to MeziVd or PVd for efficacy and safety analyses. Key eligibility criteria include age ≥18 years, 1–3 prior lines of antimyeloma treatment, prior lenalidomide exposure, minimal response or better to ≥1 prior treatment, no prior pomalidomide exposure, no proteasome inhibitor refractoriness, and documented progressive disease (PD) during or after last regimen. MeziVd arm treatment includes 21-day cycles (C) with MEZI on D1–14; 1.3 mg/m2 subcutaneous bortezomib on D1, 4, 8, and 11 of C1–8, and on D1 and 8 of ≥C9; and 20 mg oral dexamethasone on D1, 2, 4, 5, 8, 9, 11, and 12 of C1–8, and on D1, 2, 8, and 9 of ≥C9. PVd arm treatment includes 21-day cycles with 4mg oral pomalidomide on D1–14 plus Vd as administered in the MeziVd arm. Treatment continues until PD or unacceptable toxicity. Primary efficacy endpoint is progression-free survival (PFS). Planned interim analyses are for MEZI dose selection, and PFS futility and superiority. Secondary endpoints include determination of the recommended MEZI dose plus Vd, overall survival, overall response rate, time to and duration of response, time to progression, safety, and quality of life. Patients will be stratified by age (≤70 vs >70 years), number of prior lines of treatment (1 vs >1), and International Staging System stage at screening (I vs II vs III). Enrollment began in September 2022 and is ongoing. Funding: Bristol Myers Squibb. Keywords: RRMM, clinical trial, Phase III, trial in progress, CELMoDs MM-374 Efficacy and Safety of Elranatamab in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) and Prior B‑Cell Maturation Antigen (BCMA)‑Directed Therapies: Pooled Analysis From MagnetisMM Studies Ajay K. Nooka MD1, Alexander M. Lesokhin MD2, Mohamad Mohty MD3, Ruben Niesvizky MD4, Christopher Maisel MD5, Bertrand Arnulf MD6, Sarah M. Larson MD7, Asya Nina Varshavsky-Yanovsky MD, PhD8, Xavier Leleu MD9, Lionel Karlin MD10, David H. Vesole MD, PhD11, Nizar J. Bahlis MD12, Carlos Fernández de Larrea MD13, Noopur Raje MD14, Eric Leip PhD15, Umberto Conte PharmD16, Mohamed Elmeliegy PhD17, Andrea Viqueira MD18, Salomon Manier MD19 1Winship Cancer Institute, Atlanta, USA. 2Division of Hematology and Oncology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College, New York, USA. 3Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France. 4Weill Cornell Medical College - New York Presbyterian Hospital, New York, USA. 5Baylor University Medical Center, Dallas, USA. 6Hôpital SaintLouis, Paris, France. 7University of California Los Angeles Medical Center, Los Angeles, USA. 8Fox Chase Cancer Center, Philadelphia, USA. 9Centre Hospitalier Universitaire de Poitiers, Poitiers, France. 10Centre Hospitalier Lyon, Lyon, France. 11John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, USA. 12Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada. 13Hospital Clinic de Barcelona, Barcelona, Spain. 14Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA. 15Pfizer Inc, Cambridge, USA. 16Pfizer Inc, New York, USA. 17Pfizer Inc, San Diego, USA. 18Pfizer SLU, Madrid, Spain. 19Lille University Hospital, Lille, France Context: Studies with elranatamab, a BCMA/CD3 bispecific antibody, enrolled patients treated with prior BCMA-directed therapies. Objective: Outcomes in patients with RRMM and prior exposure to BCMA-directed therapy who received elranatamab. Design and Setting: Pooled analysis (MM-1, NCT03269136; MM-3, NCT04649359; MM-9, NCT05014412). Data from ~10 months after last-patient-initial-dose. Phase I and II. Patients: Eligible patients received ≥1 PI, 1 IMiD, 1 anti-CD38 antibody, and 1 BCMA-directed therapy. Interventions: MM-1 (n=13): subcutaneous (SC) elranatamab 215−1000 µg/kg; MM‑3 (n=64) and MM-9 (n=9): recommended Phase II dose, SC 76 mg QW. Main Outcome Measures: Efficacy endpoints assessed by investigator per International Myeloma Working Group criteria. Treatment-emergent adverse events (TEAEs) evaluated by Common Terminology Criteria for Adverse Effects (MM-1, v4.03; MM-3 and MM-9, v5.0); cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) graded by American Society for Transplantation and Cellular Therapy criteria. Results: 86 patients included. At baseline: 69.8%, Eastern Cooperative Oncology Group performance status ≥1; 24.4%, highrisk cytogenetics; 54.7%, extramedullary disease; median of 7.0 (range, 3−19) prior lines of therapy, including BCMA-directed antibody-drug conjugate (67.4%) and chimeric antigen receptor T cells (41.9%); 96.5% and 54.7%, triple-class and penta-drug refractory. After a median follow-up of 10.3 months (0.3−32.3): median duration of treatment, 3.3 months (0.03−30.4). At data cutoff, 24.4% of patients remained on treatment; most common reason for permanent discontinuation, progressive disease (44.2%). Overall response rate, 45.3% (95% CI 34.6−56.5); ≥ complete response in 17.4% of patients. Among responders, median time to objective response: 1.9 months (0.3−9.3). Median duration of response (DOR) was not reached by 10 months; DOR rate at 9 months, 72.4% (95% CI: 54.7−84.2). Median progression-free survival, 4.8 months (95% CI 1.9−7.7); median overall survival, not reached by 10 months (60.1% (95% CI 48.9−69.6) at 9 months). Most common (≥25% of patients) TEAEs: CRS (65.1% [G3 1.2%]), anemia (59.3% [G3/4, 46.5%]), neutropenia (44.2% [G3/4, 40.7%]), thrombocytopenia
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