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

Bonnie S. Glisson, Rom S. Leidner, Robert L. Ferris, John Powderly, Naiyer A. Rizvi, Bhumsuk Keam, Reva Schneider, Sanjay Goel, James P. Ohr, Jennifer Burton, Yanan Zheng, Steven Eck, Matthew Gribbin, Katie Streicher, Danielle M. Townsley, Sandip Pravin Patel

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Purpose: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-inhuman study evaluated MEDI0562 in adults with advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label, single-arm, dose-escalation (3þ3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. Results: In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2-48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67þ CD4þ and CD8þ memory T-cell proliferation in the periphery and decreased intratumoral OX40þ FOXP3þ cells. Conclusions: MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.

Original languageEnglish (US)
Pages (from-to)5358-5367
Number of pages10
JournalClinical Cancer Research
Issue number20
StatePublished - Oct 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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