Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: a Phase I Study.

Purpose: The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody (mAb) targeting effector regulatory T cells (eTregs), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab. Experimental Design: This was a multicenter, phase I, dose-escalation study, followed by disease specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab or tremelimumab in patients with advanced solid tumors. Cohort expansion occurred with mogamulizumab 1 mg/kg plus durvalumab 10 mg/kg or tremelimumab 10 mg/kg in patients with advanced pancreatic cancer. Results: Forty patients were enrolled during dose escalation, followed by 24 patients during dose expansion. No dose-limiting toxicities occurred during dose escalation. No new or unexpected toxicities were seen. Tolerability, the primary endpoint, was acceptable utilizing mogamulizumab 1 mg/kg plus durvalumab or tremelimumab 10 mg/kg in the combined dose-escalation and dose-expansion cohorts (each n = 19). At these doses, the objective response rate was 5.3% (95% CI: 0.1%, 26.0%) [1 partial response] with each combination treatment. At all doses, mogamulizumab treatment led to almost complete depletion of peripheral eTregs as well as reduction of intratumoral Tregs in the majority of patients. There was no clear correlation of clinical response with peripheral or intratumoral reduction in CCR4+ eTregs or with baseline degree of CCR4+ expression. Conclusions: Mogamulizumab in combination with durvalumab or tremelimumab did not result in potent antitumor efficacy in patients with advanced solid tumors. Tolerability of mogamulizumab 1 mg/kg combined with durvalumab or tremelimumab 10 mg/kg was acceptable.