EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer

PRIMARY OBJECTIVES: I. To evaluate the maximum tolerated dose (MTD) and to establish the recommended phase II dose (RP2D) of EMB-01 given in combination with osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). (Phase Ib) II. To preliminarily assess efficacy and further evaluate the safety and tolerability of EMB-01 plus osimertinib at the RP2D in advanced EGFR-mutant NSCLC patients who progressed on prior EGFR tyrosine kinase inhibitor (TKI) treatment. The primary endpoint is objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II) SECONDARY OBJECTIVES: I. To assess the pharmacokinetics (PK) of EMB-01 and osimertinib. II. To assess the immunogenicity of EMB-01 and osimertinib. III. To evaluate preliminary antitumor activity of EMB-01 and osimertinib. (Phase I) IV. To continue to evaluate the antitumor activity of EMB-01 and osimertinib such as progression free survival, best overall response, duration of response, and clinical benefit rate. (Phase II) EXPLORATORY OBJECTIVES: I. To explore the relationships between pharmacokinetics, biomarkers, adverse event profiles, and anticancer activity of EMB-01 combined with osimertinib. OUTLINE: This is a phase Ib, dose-escalation study of EMB-01 and osimertinib followed by a phase II study. Patients receive EMB-01 intravenously (IV) weekly. Patients also receive osimertinib orally (PO) once daily (QD) on days 1-28. Treatment cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. After the completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.