Safety, toxicity and activity of multi-kinase inhibitor vandetanib in combination with everolimus in advanced solid tumors.

Abstract

9073Background: RET gene aberrations have been identified in several types of cancer, including lung, thyroid, colon and breast cancers. Inhibition of RET signaling in preclinical tumor models using vandetanib (VAN), a TKI that targets VEGFR2/EGFR and RET, in combination with everolimus (EV), an mTOR inhibitor, was found to overcome intrinsic and /or acquired tumor resistance to either agent alone, suggesting the combined therapy warrants investigation in patients. Methods: A “3+3” dose escalation and expansion trial was designed to determine the safety, maximum tolerated dose , recommended Phase II dose (RP2D), dose-limiting toxicities (DLTs) and activity of VAN+EV in advanced/refractory solid tumors. Tumor responses were assessed by RECIST. The molecular correlates of clinical response were analyzed by next generation sequencing (NGS) and/or FISH if available. Results: Among the 96 pts treated to date, median age was 56 years (18-82 yrs) and 43 pts (45%) were male. Most common diagnoses were sarcoma (20...