BACKGROUND: Given the incurable nature of multiple myeloma (MM), efforts are made to improve the efficacy of anti-CD38 monoclonal antibodies via combinations with other potentially synergistic therapies. This Phase 1/2 trial (NCT03194867) was designed to determine whether cemiplimab (anti-PD-1) enhances the anti-myeloma activity of isatuximab (anti-CD38) in patients with relapsed and refractory multiple myeloma (RRMM), to confirm the feasibility of the combination, determine its efficacy, and further evaluate its safety. METHODS: Patients received isatuximab 10 mg/kg once weekly for 4 weeks followed by every 2 weeks (Isa), or isatuximab 10 mg/kg plus cemiplimab 250 mg every 2 (Isa + CemiQ2W) or every 4 weeks (Isa + CemiQ4W). RESULTS: Overall, 106 patients with RRMM treated with a median of 4 prior lines were included; 25.5% had high-risk cytogenetics, 63.2% were refractory to proteasome inhibitors and immunomodulatory agents, 26.4% were previously exposed to daratumumab, and 84.0% were refractory to their last treatment line. There were no major changes in the safety or pharmacokinetic profile of isatuximab with the addition of cemiplimab. As assessed by investigators, four patients (11.8%) in the Isa arm, nine patients (25.0%) in the Isa + CemiQ2W arm, and eight patients (22.2%) in the Isa + CemiQ4W arm were responders. Though response rates were numerically higher in cemiplimab-containing arms, differences were not statistically significant and did not translate to improved progression-free or overall survival after a median follow-up of 9.99 months. CONCLUSION: Our results suggest a marginal benefit by adding cemiplimab to isatuximab, despite demonstration of target engagement, without additional observed safety issues.

Centre Hospitalier Universitaire de Sherbrooke Division of Hematology and Medical Oncology Université de Sherbrooke Sherbrooke Canada

Centro Integrado de Hematologia e Oncologia Hospital Mãe de Deus Porto Alegre Brazil

Department of Biomedical Sciences Humanitas University Rozzano Milan Italy

Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens Greece

Department of Haematology Wollongong Hospital Wollongong New South Wales Australia

Department of Hematology ASST Spedali Civili di Brescia Brescia Italy

Department of Hematology Gustave Roussy Université Paris Saclay Villejuif France

Department of Hematology Hôpital Lyon Sud Hospices Civils de Lyon Université Claude Bernard Lyon 1 Lyon France

Department of Internal Medicine University Hospital Brno Brno Czech Republic

Department of Medicine Division of Hematology University of Colorado School of Medicine Aurora Colorado USA

Department of Oncology and Hematology IRCCS Humanitas Research Hospital Rozzano Milan Italy

Division of Hematological Malignancies and Cellular Therapeutics University of Kansas Lawrence Kansas USA

Division of Hematology Oncology and Transplantation Department of Medicine Maisonneuve Rosemont Hospital Université de Montréal Montréal Qubec Canada

Hematology Department CHU Nantes Nantes France

Hôpital du Sacré Coeur de Montréal Montréal Qubec Canada

Myeloma Service Department of Medicine Memorial Sloan Kettering Cancer Center New York City New York USA

Sanofi Beijing China

Sanofi Cambridge Massachusetts USA

Sanofi Clinical Pharmacokinetics on behalf of Excelya Chilly Mazarin France

Sanofi Research and Development Chilly Mazarin France

Sanofi Research and Development on behalf of Altran Vitry sur Seine France

Sanofi Research and Development Vitry sur Seine France

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