Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors

The primary objective of Phase 1 is to assess safety and tolerability, determine the recommended phase 2 dose (RP2D) and assess the pharmacokinetics of RXDX-106. The secondary objective is to evaluate the preliminary antitumor activity of RXDX-106, as assessed by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Immune Response Related Criteria in Solid Tumors (iRECIST) in patients with advanced or metastatic solid tumors. The proposed starting dose of RXDX-106 was calculated based upon nonclinical toxicology studies to determine a recommended first-in-human starting dose, which may be below the biologically active level. Therefore, in order to minimize the number of patients treated at this dose, an accelerated titration design will be used for the first cohort, after which, a conventional 3+3 scheme will be followed for enrollment in subsequent dose levels. Final determination of the single agent RP2D will be based on available safety, tolerability, PK, pharmacodynamics, and efficacy data from different dose levels and schedules tested, but will be no higher than the maximum tolerated dose. After RP2D has been determined, additional expansion cohorts of patients (up to 15) with specific tumor types, treatment history, and/or expression of a specific biomarker may be enrolled.