Safety and tolerability of MEDI0562, an OX40 agonist monoclonal antibody, in combination with durvalumab or tremelimumab in adult patients with advanced solid tumors.

PURPOSE: Combination therapies targeting immunological checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 monoclonal antibody, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors.

EXPERIMENTAL DESIGN: In this phase 1, multicenter, open-label study, patients received escalating doses of MEDI0562 (2.25, 7.5, or 22.5 mg) every two weeks (Q2W) in combination with durvalumab (1500 mg) or tremelimumab (75 or 225 mg) Q4W, intravenously, until unacceptable toxicity or progressive disease. Tumor assessments were performed Q8W. The primary objective was to evaluate safety and tolerability.

RESULTS: Among the 27 and 31 patients who received MEDI0562 + durvalumab or MEDI0562 + 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 maximum tolerated dose of MEDI0562 + durvalumab was 7.5 mg MEDI0562 + 1500 mg durvalumab; the maximum administered dose of MEDI0562 + tremelimumab was 22.5 mg MEDI0562 + 225 mg tremelimumab. Three patients in the MEDI0562 + durvalumab arm had a partial response. The mean percentage of Ki67+CD4+ and Ki67+CD8+ memory T cells increased by >100% following the first dose of MEDI0562 + durvalumab or tremelimumab in all dose cohorts. A decrease in OX40+FOXP3 T regulatory 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.