Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors

Purpose: Combination therapies targeting immunologic checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1_K OX40 mAb, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label study, patients received escalating doses of MEDI0562 (2.25, 7.5, or 22.5 mg) every 2 weeks in combination with durvalumab (1,500 mg) or tremelimumab (75 or 225 mg) every 4 weeks, intravenously, until unacceptable toxicity or progressive disease. Tumor assessments were performed every 8 weeks. The primary objective was to evaluate safety and tolerability. Results: Among the 27 and 31 patients who received MEDI0562 þ durvalumab or MEDI0562 þ tremelimumab, 74.1% and 67.7% reported a treatment-related adverse event (AE), and 22.2% and 19.4% experienced a treatment-emergent AE that led to discontinuation, respectively. The MTD of MEDI0562 þ durvalumab was 7.5 mg MEDI0562 þ 1,500 mg durvalumab; the maximum administered dose of MEDI0562 þ tremelimumab was 22.5 mg MEDI0562 þ 225 mg tremelimumab. Three patients in the MEDI0562 þ durvalumab arm had a partial response. The mean percentage of Ki67^þCD4^þ and Ki67^þCD8^þ memory T cells increased by >100% following the first dose of MEDI0562 þ durvalumab or tremelimumab in all dose cohorts. A decrease in OX40^þFOXP3 regulatory T cells was observed in a subset of patients with available paired biopsies. Conclusions: Following dose escalation, moderate toxicity was observed in both treatment arms, with no clear efficacy signals demonstrated.