This is a phase 1b/2 study, designed to evaluate the safety, tolerability, and efficacy of VX15/2503 in combination with avelumab in subjects diagnosed with advanced (stage IIIB/IV) NSCLC who have either progressed on first or second-line systemic anticancer therapy or who have declined treatment with first or second-line system anticancer therapy. The primary objective (Dose Escalation Phase) is to evaluate the safety and tolerability of ascending doses of VX15/2503 Q2W in combination with avelumab 10mg/kg Q2W. The second primary objective (Dose Expansion Phase) is to evaluate safety and tolerability of the recommended phase 2 dose of VX15/2503 administered in combination with 10 mg/kg avelumab Q2W. The secondary objectives include (Dose Expansion Phase), a preliminary estimate of efficacy using the following in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, Objective Response (OR), Duration of Response (DoR) and Progression-Free Survival (PFS), as well as making a preliminary estimate of efficacy using the following in accordance with iRECIST, OR, DoR and PFS. Additional secondary objectives are to characterize the pharmacokinetics profile of VX15/2503 and avelumab administered Q2W in combination, evaluate the immunogenicity of VX15/2503 and avelumab administered Q2W and evaluate VX15/2503 and avelumab pharmacodynamics markers including but not limited to receptor occupancy. Exploratory objectives include identification of candidate biomarkers of activity and biomarkers that may predict response to treatment with combination therapy of VX15/2503 and avelumab.~Enrollment will involve approximately 62 individuals who are 18 years of age or older with advanced non-small cell lung cancer. The study will be divided into two phases, dose escalation with up to 18 Immunotherapy naive subjects and dose expansion with up to 50 subjects (up to 22 subjects that are Immunotherapy naive and up to 28 subjects that have failed on Immunotherapy). Subjects that are enrolled in the dose escalation phase may continue into the dose expansion phase, as long as there is no evidence of disease progression. The subjects entering the dose expansion phase from dose escalation, may have their dose increased to the recommend phase 2 dose, once it is determined. Any subjects that have evidence of disease progression will be taken off of treatment and will have a post treatment safety follow-up visit 10 weeks after last treatment. Subjects that have discontinued study drug will also continue to be followed every 3 months for survival, or lost to follow-up. It is estimated that the study will take approximately 33 months between first subject enrolled and last subject visit.
The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in combination with a fixed dose of avelumab in patients with advanced non-small cell lung cancer. The dose escalation portion of the study will determine the maximum tolerated dose (MTD) of VX15/2503 administered in combination with avelumab.