TPS2605 Background: HuMax-AXL-ADC is an antibody-drug conjugate (ADC) composed of an Axl-specific human monoclonal immunoglobulin G1 (IgG1κ) conjugated via a protease-cleavable valine-citrulline linker to the microtubule disrupting agent monomethyl auristatin E (MMAE). In vivo, HuMax-AXL-ADC demonstrated therapeutic anti-tumor efficacy in patient-derived xenograft models representing a variety of solid cancers, including pancreas, thyroid, lung, esophageal, cervical cancers and malignant melanoma. The non-clinical safety profile and pharmacokinetics (PK) of a once every 3 weeks (1Q3W) dosing schedule were established in cynomolgus monkeys. Methods: The primary objective of this trial is to determine the MTD and to establish the safety profile of HuMax-AXL-ADC in a mixed population of patients with specified solid tumors: ovarian, cervical, endometrial, thyroid cancer, NSCLC, and malignant melanoma. The trial consists of two parts, a phase I dose escalation part and a phase IIa expansion part. The dose escalation part explores two different dosing regimens: the first investigates doses from 0.3 up to 2.8 mg/kg to be administered 1Q3W. The second investigates doses in the range of 0.45 to 1.4 mg/kg to be administered weekly for 3 weeks followed by one treatment-free week (3Q4W dosing schedule). The second arm has a delayed start to inform a safe starting dose: when at least 8 patients have been evaluated for dose limiting toxicities, the 1.5 mg/kg cohort of the 1Q3W arm has been declared safe, and the predicted PK parameters of the starting dose in the 3Q4W arm are below pre-defined limits, the 3Q4W arm will be initiated. The 1Q3W arm follows a modified Bayesian Continuous Reassessment Method including escalation with overdose control in up to 41 patients on up to 7 main and 4 intermediate dose levels while the 3Q4W arm is run as a standard 3+3 trial design on up to 5-6 dose levels. In the phase IIa expansion part, further safety and biological activity data will be generated in selected indications using cohorts of 22 patients (11+11 patients in each cohort applying the Simon’s two-stage design). Clinical trial information: NCT 02988817.