Study of the CD40 Agonistic Monoclonal Antibody APX005M

Phase 1 Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Subjects With Solid Tumors

This study is a phase 1 open-label dose escalation study of the immuno-activating monoclonal antibody APX005M in adults with solid tumors. Study is intended to establish the maximum tolerated dose and the overall safety and tolerability of APX005M in 3 different administration schedules.

APX005M-001 is an open-label study and comprises a dose-escalation portion of approximately 8 dose level cohorts, plus an expansion cohort.

Eligible subjects with solid tumors will receive intravenous APX005M every 3 week, every 2 week or every 1 week until disease progression, unacceptable toxicity or death, whichever occurs first.

Study objectives include:

• Evaluate safety of APX005M
• Determine the maximum tolerated dose of APX005M
• Determine the pharmacokinetic parameters of APX005M: the maximal drug concentration (Cmax), area under the curve of serum concentration over time (Area Under the Curve/ AUC), and half-life (t½).
• Preliminary assessment of clinical response

Key Inclusion Criteria:

• Histologically documented diagnosis of solid tumor
• For subjects in the every 2 week and every 1 week dosing cohorts histologically or cytologically documented diagnosis of urothelial carcinoma, melanoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, or any solid tumor with high microsatellite instability status (MSI-high)
• No known effective therapy options are available
• Measurable disease by RECIST 1.1
• ECOG performance status of 0 or 1
• Adequate bone marrow, liver and kidney function
• No toxicities related to prior treatment related toxicities with the exception of alopecia and neuropathy
• Negative pregnancy test for women of child bearing potential

Key Exclusion Criteria:

• Any history of or current hematologic malignancy
• Major surgery or treatment with any other investigational agent within 4 weeks
• Uncontrolled diabetes or hypertension
• History of arterial thromboembolic event
• History of congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction
• Active known clinically serious infections