Int J Infect Dis

. 2022 Aug 17;S1201-9712(22)00475-1.
doi: 10.1016/j.ijid.2022.08.007. Online ahead of print.
Pembrolizumab in combination with tocilizumab in high-risk hospitalized COVID-19 patients (COPERNICO): A randomized proof-of-concept phase II study

Matilde Sánchez-Conde 1 , Pilar Vizcarra 1 , José Manuel Pérez-García 2 , María Gion 3 , María Pilar Martialay 4 , Javier Taboada 5 , Alberto Alonso-Fernández 6 , Miguel Sampayo-Cordero 7 , Andrea Malfettone 7 , Isabel Tena 7 , Sergio De La Torre 8 , Antonio Llombart-Cussac 9 , Javier Cortés 10



Objectives: Severe coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated IL-6). Pembrolizumab (P; immune-activating anti-PD-1 antibody) plus tocilizumab (TCZ; anti-IL6 receptor antibody) might interrupt the hyperinflammation and restore cellular immunocompetence. We assessed the efficacy and safety of P+TCZ+standard of care [SOC] in high-risk, hospitalized COVID-19 pneumonia patients without mechanical ventilation.
Methods: Randomized, controlled, open-label, phase 2 trial in patients with severe SARS-CoV-2-infection to assess the hospitalization period to discharge.
Results: Twelve patients were randomized (P+TCZ+SOC, n=7; SOC, n=5). Nine (75%) were males, with a median age of 68 (41-79) years. The median time to discharge for P+TCZ+SOC and SOC was 10 and 47.5 days (p=0.03), with 0 (n=1 patient had P-related grade 5 myositis) and 2 COVID-19-related deaths, respectively.
Conclusions: The addition of P and TCZ to SOC reduced the hospitalization period, with higher and faster discharges without sequelae than SOC alone.

Keywords: COVID-19; Pembrolizumab; SARS-CoV-2-infection; tocilizumab.