Background: AXL kinase has emerged as a key regulator of the epithelial to mesenchymal transition (EMT), a process that enables cancer cells to develop migratory and invasive properties and acquire resistance to chemotherapeutics and targeted agents. AXL kinase is also known to serve to dampen the immune response to dying tumor cells. By activating EMT, AXL signaling allows cancer cells to engulf neighboring cancer cells undergoing apoptosis, reducing presentation of pro-inflammatory stimuli to the immune system. Consequently, the inhibition of AXL by TP-0903 may potentially reduce cancer cell metastasis, target cancer cells that demonstrate immunity to chemotherapeutics and activate the anti-cancer immune response. Methods: Patients with advanced solid tumors that are refractory or intolerant to established therapy have been enrolled in a standard 3+3 dose escalation trial of TP-0903 given orally once daily for 21 days of a 28-day cycle. Cohort dose levels 1 through 5 have been completed without DLT, enrollment into cohort 6 began January 2018. The primary objective is to determine the MTD and DLTs; secondary objectives are PK, radiographic response, PD activity (e.g. GAS6/AXL and other EMT markers), biological activity and RP2D. Key eligibility criteria include age ≥ 18 years, ECOG ≤1, adequate organ function, life expectancy of > 3 mos. Once the MTD has been reached, the study will be expanded into 5 cohorts of 20 patients each: 1) Patients on immunotherapy who demonstrate progression but are clinically stable, 2) EGFR + NSCLC having progressed on ≤ 2 lines of TKIs, 3) BRAF, KRAS or NRAS mutated CRC with no standard therapy remaining, 4) Platinum refractory/resistant ovarian, 5) BRAF mutated melanoma that hasn’t responded to immunotherapy or combination BFAF/MEK inhibitor. Patients will be biopsied in each cohort to explore changes to the EMT phenotype. Clinical trial information: NCT02729298