Background: Inhibition of Mer Proto-oncogene tyrosine kinase (MERTK) and AXL may lower the threshold for immune activation thereby promoting anti-tumor activity. PF-07265807 (ARRY-067) is a selective small-molecule inhibitor of the tumor-associated macrophage kinases MERTK and AXL. In preclinical models, PF-07265807 plus anti-programmed cell death protein 1 (anti-PD-1) antibodies show antitumor activity that results in long-term cures and resistance to tumor re-challenge. Sasanlimab is a monoclonal antibody to PD-1 administered subcutaneously (300 mg every 4 wk or equivalent); it has an acceptable safety profile and is being tested in a Phase 3 trial in non-muscle invasive bladder cancer. This first-in-human study will evaluate safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of PF-07265807 alone and with sasanlimab in patients (pts) with selected advanced or metastatic solid tumors. Study design of PF-07265807 monotherapy dose escalation (Part 1) was presented at ASCO 2021 (TPS2671). Here, we describe dose escalation (Part 2) and dose expansion (Part 4) cohorts for the doublet combination of PF-07265807 + sasanlimab. Methods: This is a Phase 1, open-label, multi-center study (NCT04458259) of PF-07265807. Adult pts with selected advanced or metastatic solid tumors who are intolerant or resistant to standard therapy will enroll into doublet therapy dose escalation (Part 2). Pts who are anti-PD-1/PD-L1 treatment naïve with intermediate tumor mutational burden (defined as ≥6 and < 16 microsatellite stable) colorectal cancer (CRC) or PD-L1+ (defined as combined positive score ≥1) gastric cancer will enroll into doublet therapy dose expansion cohorts (Part 4). Other key eligibility criteria: measurable or non-measurable disease by RECIST 1.1; ECOG PS 0–2; adequate bone marrow, renal and liver function; and resolved acute effects of any prior therapy. Each cycle will be 21 days. Treatment will continue until disease progression or unacceptable toxicity, whichever occurs first. The doublet maximum tolerated dose (MTD) will be guided by a Bayesian analysis of dose limiting toxicity (DLT) data for doublet therapy (Part 2). The recommended phase 2 dose (RP2D) will then be determined via holistic data review with/without the MTD identification. Primary endpoints in Part 2 include the incidence of DLTs, adverse events and laboratory abnormalities. After doublet MTD/RP2D is identified in Part 2, the preliminary anti-tumor activity of PF-07265807 + sasanlimab will be explored in Part 4. Primary endpoints in Part 4 include objective response and complete response rates; secondary endpoints include disease control rate and response duration, adverse events and laboratory abnormalities. The study began in Q4 2020 and is recruiting pts. Clinical trial information: NCT04458259.