Safety and clinical activity of MEDI0562, a humanized OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors

Abstract

Background:MEDI0562, a humanized IgG4 OX40 monoclonal antibody, demonstrated a manageable safety profile and pharmacologic activity in preliminary analyses of the Phase 1 study (NCT02318394) in pts with advanced solid tumors.1 Here we present updated safety data and clinical activity for pts treated during the dose-escalation phase. Methods: Pts were treated with one of 6 escalating doses of MEDI0562 (0.03, 0.1, 0.3, 1.0, 3.0, and 10 mg/kg) every 2 weeks (Q2W) until confirmed disease progression or unacceptable toxicity. Tumor assessments were performed every 8 weeks with immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Results: A total of 55 pts received MEDI0562 across 6 dose cohorts (3+ 3 design), with a maximum administered dose of 10 mg/kg Q2W and no DLTs observed. Median duration of exposure was 10 (2 to 48) weeks. Adverse events (AEs) and treatment-related AEs (trAEs) were reported in 96% and 67% of pts, respectively; the most common trAEs were fatigue (31%) and infusion-related reaction (15%). Gr 3 trAEs occurred in 16% of pts with the most common being pyrexia (4%); 53% of pts had trAEs of Gr1 or 2, with no apparent dose relation. There were no trAEs leading to discontinuation or Gr 4 or 5 trAEs. Of 50 response evaluable pts, 2 pts (sq cell carcinoma of the larynx - 0.03 mg/kg Q2W and bladder cancer - 3 mg/kg Q2W) had irPR at the first tumor assessment, with an overall survival of 13.8 and 10.2+ mos, respectively. Stable disease was seen in 22 (44%) pts with SD in 20 pts lasting >3 mos. Serum exposure of MEDI0562 increased approximately dose proportionally. Posttreatment antidrug antibody (ADA) was detected in 26 (51%) of 55 pts. ADA exhibited variable impact on PK exposure at all doses below 3 mg/kg. A 1.5 to 3.0-fold increase in mean peaks of the percentage of peripheral Ki67+ CD4+ and Ki67+ CD8 +memory T cells was observed across ascending dose levels. Conclusions: MEDI0562 was generally well tolerated in adult pts with advanced solid tumors and exhibited clinical and pharmacological activity. Based on the ADA data, a suggested MEDI0562 Phase 2 dose of≥3 mg/kg Q2W was selected.