Pembrolizumab in combination with tocilizumab in high-risk hospitalized patients with COVID-19 (COPERNICO): A randomized proof-of-concept phase II study

Int J Infect Dis. 2022 Oct;123:97-103. doi: 10.1016/j.ijid.2022.08.007. Epub 2022 Aug 17.

Abstract

Objectives: Severe COVID-19 is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated interleukin 6. Pembrolizumab (P; immune-activating anti-programmed cell death-1 antibody) plus tocilizumab (TCZ; anti- interleukin 6 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 patients with COVID-19 pneumonia without mechanical ventilation.

Methods: Randomized, controlled, open-label, phase II trial in patients with severe SARS-CoV-2 infection to assess the hospitalization period to discharge.

Results: A total of 12 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 zero (n = 1 patient had P-related grade 5 myositis) and two COVID-19-related deaths, respectively.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized
  • COVID-19 Drug Treatment*
  • Female
  • Humans
  • Interleukin-6
  • Male
  • Proof of Concept Study
  • Receptors, Interleukin-6
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • pembrolizumab
  • tocilizumab