Background: MERTK is a receptor tyrosine kinase from the tumor-associated macrophage kinase (TAMK) family that regulates key aspects of immune homeostasis and responses to infection. MERTK inhibition may lower the threshold for immune activation thereby promoting anti-tumor activity. Agents with some degree of MERTK inhibitory activity have been investigated in the clinic, but are limited by poor potency in patients (pts) and significant off-targets effects. PF-07265807 (ARRY-067) is a selective small-molecule inhibitor of the TAMKs MERTK and AXL. In preclinical models, PF-07265807 monotherapy shows antitumor activity that results in long-term cures and resistance to tumor re-challenge when combined with anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibodies. This first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of PF-07265807 in pts with selected advanced or metastatic solid tumors. This study will also explore the potential utility of PF-07265807 in combination with anti-PD-1/PD-L1 antibodies. Methods: This is a phase 1, open-label, multi-center, dose-escalation study (NCT04458259) to evaluate the safety, PK and tolerability of PF-07265807. Eligible participants will be adult pts with selected advanced or metastatic solid tumors who are intolerant or resistant to standard therapy. Other key eligibility criteria: measurable disease by RECIST 1.1 or non-measurable disease; Eastern Cooperative Oncology Group performance status 0–2; adequate bone marrow, renal and liver function; and resolved acute effects of any prior therapy. Successive cohorts of pts will receive escalating doses of PF-07265807 starting from 25 mg QD. Each cycle will be 21 days in duration (14 days on/7 days off). Study drug treatment will continue until disease progression or unacceptable toxicity, whichever occurs first. For dose escalation, a Bayesian logistic regression model will be used to model the relationship of dose-limiting toxicities (DLTs) to PF-07265807 dose. This model, along with escalation with overdose control, will guide the dose escalation of PF-07265807 after the completion of the DLT observation period (first two cycles of treatment, i.e. 42 days) of each cohort, until determination of the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D). After the MTD/RP2D is identified, the safety and efficacy of combined PF-07265807 and anti-PD1/PD-L1 treatment will be explored. Primary endpoints: incidence of DLTs, treatment-emergent adverse events and laboratory abnormalities. Secondary endpoints: PK parameters of PF-07265807, objective response rate and duration of response. The study began enrolling pts in September 2020 and is still recruiting. Clinical trial information: NCT04458259