Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors

Clin Cancer Res. 2022 Feb 1;28(3):479-488. doi: 10.1158/1078-0432.CCR-21-2781. Epub 2021 Nov 9.

Abstract

Purpose: The aim of the study was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody targeting effector regulatory T cells (Treg) in combination with the checkpoint inhibitor nivolumab in patients with locally advanced or metastatic solid tumors.

Patients and methods: This was a multicenter, dose-finding (phase I), and dose expansion (phase II) study (NCT02705105) in patients with locally advanced or metastatic solid tumors. There were no dose-limiting toxicities in phase I with mogamulizumab 1 mg/kg every week for cycle 1 followed by 1 mg/kg every 2 weeks plus nivolumab 240 mg every 2 weeks intravenously, and cohort expansion occurred at this dose level.

Results: All 114 patients treated with mogamulizumab 1 mg/kg plus nivolumab 240 mg in phases I (n = 4) and II (n = 110) were assessed for safety and efficacy. Mogamulizumab plus nivolumab showed acceptable safety and tolerability. Objective response rate was 10.5% [95% confidence interval (CI), 5.6-17.7; 3 complete and 9 partial responses]. Disease control rate was 36.8%. Median duration of response was 14.4 months. Median progression-free survival was 2.6 (95% CI, 2.3-3.1) months, and median overall survival was 9.5 (95% CI, 5.9-13.5) months.

Conclusions: Combination of mogamulizumab with nivolumab for treatment of patients with locally advanced or metastatic solid tumors did not result in enhanced efficacy. Tolerability of mogamulizumab 1 mg/kg plus nivolumab 240 mg was acceptable.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Nivolumab / administration & dosage*
  • Progression-Free Survival
  • Safety
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • Nivolumab
  • mogamulizumab