Safety
death, myalgia, DLTs, Cemi, TEAEs, pain, pulmonary sepsis, Treatment‐related TEAEs, TEAE
INFUSION REACTION, DISEASE, UPPER RESPIRATORY TRACT INFECTION, ADVERSE EVENT, SEPTIC SHOCK, INFUSION REACTION
No DLTs were observed during the Phase 1 portion of the study. The all‐treated/safety population comprised 33 patients treated with Isa alone, 37 patients treated with Isa + CemiQ2W, and 35 patients treated with Isa + CemiQ4W (two patients were randomized to a treatment arm but received another one, so they were kept in the randomized arm). The median number of cycles (range) started by patients was 4 (1–12) in the Isa arm, 3 (1–14) in the Isa + CemiQ2W arm, and 4 (1–15) in the Isa + CemiQ4W arm. At the time of data cutoff, the median duration of exposure (range) to isatuximab was 14.43 weeks (2.0–48.0) in the Isa arm, 12.57 weeks (1.0–59.4) in the Isa + CemiQ2W arm, and 14.29 weeks (3.0–62.9) in the Isa + CemiQ4W arm. The median duration of exposure (range) to cemiplimab was 12.57 weeks (2.0–59.4) in the Isa + CemiQ2W arm and 16.29 weeks (4.0–62.9) in the Isa + CemiQ4W arm.At least 1 treatment‐emergent adverse event (TEAE) was reported in 100% of the Isa arm, 97.3% of the Isa + CemiQ2W arm, and 94.3% of the Isa + CemiQ4W arm (Table Overview of TEAEs (All‐treated/safety population).Abbreviations: Cemi, cemiplimab; IR, infusion reaction; Isa, isatuximab; Q2W, every 2 weeks; Q4W, every 4 weeks; SAE, serious adverse event; TEAE, treatment‐emergent adverse event.Grade 5 TEAEs during the on‐treatment period included: Isa−disease progression (TEAEs leading to discontinuation included: Isa + CemiQ2W–myalgia (Treatment‐related TEAEs are TEAEs related to at least one drug of the combination.Summary of TEAEs occurring in at least 15% of patients (All‐treated/safety population).Abbreviations: Cemi, cemiplimab; Isa, isatuximab; Q2W, every 2 weeks; Q4W, every 4 weeks.One patient in the Isa + CemiQ4W arm experienced a Grade 3 infusion reaction leading to hospitalization and investigational medicine product discontinuation, which was mistakenly reported as a Grade 2 infusion reaction.Overall, nine patients died during the on‐treatment period. The main reason for death was due to progressive disease, including one patient in the Isa arm, two patients in the Isa + CemiQ2W arm, and two patients in the Isa + CemiQ4W arm. Overall, four patients in the Isa + CemiQ4W arm experienced a fatal TEAE during the on‐treatment period. Among them, one patient had pulmonary sepsis related to study treatment and three patients had fatal TEAEs unrelated to study treatment, including upper respiratory tract infection, euthanasia (the patient asked for euthanasia due to uncontrollable pain in the context of progressive disease), and septic shock. There was one TEAE‐related death during the post‐treatment period.Infusion reactions (IRs) of any grade were experienced by 18 patients (54.5%) of patients in the Isa arm, 15 patients (40.5%) in the Isa + CemiQ2W arm, and 16 patients (45.7%) in the Isa + CemiQ4W arm. There were 2 Grade 1 IRs related to cemiplimab. Details of IRs are provided in Table 