Clin Cancer Res: Immune checkpoint target drug MEDI0562 to treat advanced solid tumors.

Immune checkpoint blocking has been shown to have clinical benefits for a variety of solid tumors, but drug resistance and recurrence occur frequently, limiting the clinical use of immuno checkpoint inhibitors.
, we need to develop new immunomodulation targets that are highly expressed in activated immune cells.
MEDI0562 is an anthogenic, agitated monoclonal antibody that binds specifically to the co-stimulating molecule OX40.
study is a multi-center, open-label, single-arm, incremental dose (designed by 3-3) Phase I clinical trial, and the first human study to evaluate MEDI0562 for adult patients with advanced solid tumors.
treat patients with different doses of MEDI0562 (0.03, 0.1, 0.3, 1.0, 3.0 or 10 mg/kg.2 weeks) until the disease progresses or insulable toxicity occurs.
the main purpose of the project is to assess safety and tolerance.
end points include anti-tumor activity, pharmacodynamics, immunogenics, and pharmacodynamics.
, 55 patients received at least one dose of MEDI0562 treatment, which was included in the analysis.
type of tumor is head and neck squamous cell carcinoma (47%).
treatment duration is 10 weeks (range 2-48 weeks).
treatment-related adverse reactions (TRAEs) occurred in 67% of patients, with fatigue (31%) and infusion-related reactions (14%).
level 3 TRAEs occurred in 14% of patients, with no significant dose correlation;
two patients showed partial immune-related remission, and 44% were stable.
MEDI0562 therapy can induce the proliferation of Ki67-CD4-plus and CD8-memory T-cells that increase exodus, and reduce the proliferation of OX40-FOXXP3-plus cells in tumors.
MEDI0562 for patients with severe pre-treatment, even at doses up to 10 mg/kg, and deserve further evaluation.
.