For a study, researchers sought to assess MOXR0916, an IgG<sub style=”vertical-align: sub;”>1</sub> monoclonal anti-OX40 effector-competent agonist. Receiving intravenously once every 3 weeks was given to qualified patients with solid tumors who had either locally progressed or metastatic refractory illness (Q3W). For patients with melanoma, renal cell carcinoma, non-small cell lung carcinoma, urothelial carcinoma, and triple-negative breast cancer, a 3+3 dose-escalation stage (0.2-1,200 mg; n=34) was followed by expansion cohorts at 300 mg (n=138). The well-tolerated MOXR0916 exhibited no dose-limiting effects. No MTD was accomplished. About 95% of patients reported 1 or more adverse events (AEs); 56% of these AEs, the majority of which fell into categories 1-2, were connected to MOXR0916. Fatigue (17%), diarrhea (8%), myalgia (7%), nausea (6%), decreased appetite (6%), and infusion-related response (5%) were the most common adverse events (AEs) associated with treatment. Pharmacokinetic (PK) characteristics supported Q3W delivery and were dose-proportional between 80 and 1,200 mg. PK and OX40 receptor saturation resulted in the advised 300 mg Q3W expansion dose. PD-L1 was upregulated, and immunological activation was present in some matched tumor samples. A partial response was observed in 1 patient with renal cell carcinoma. About 33% of patients had stable disease overall. PD-1/PD-L1 antagonists should be investigated further in conjunction with MOXR0916 due to the drug’s favorable safety profile and the signs of tumor immune activation in a subgroup of patients, notwithstanding the rarity of objective responses to MOXR0916 monotherapy.

Source: aacrjournals.org/clincancerres/article/28/16/3452/707402/First-In-Human-Phase-I-Study-of-the-OX40-Agonist