Background: C019199 was designed to be a tumor immune microenvironment (TME) modulator in order to improve the efficacy against tumor growth when combined with immune checkpoint inhibitors, like anti-PD1 or anti-PD-L1. It was shown to have a specific inhibition profile against CSF-1R, DDR1 and VEGFR2 with IC₅₀ of 14nM, 40nM and 79nM, respectively. CSF-1R’s inhibition may deplete Tumor-associated macrophages (TAMs) in TME, help the infiltration of T cells and enhance T cell responses. But a single modulating mechanism may not be strong enough or may be vulnerable and easily overcome by tumors. C019199 can reshape the TME by additionally inhibiting DDRs and VEGFR2, which may remove the "physical barrier" of tumor extracellular matrix and further increase T cell infiltration on top of inducing tumor blood vessels normalization. As a single agent with the appropriate combination of multiple modulation effects, it will potentially turn "cold" tumors into "hot" tumors. Preclinical studies have shown that C019199 inhibits tumor growth in multiple animal tumor models and has better antitumor efficacy when combined with immune checkpoint blockades. Methods: A first-in-human, open label, multicenter, dose-escalation/expansion study of C019199 is currently enrolling. Eligible subjects (age ≥ 18 years and <76 years) with histologically or cytologically confirmed relapsed, refractory, or progressive metastatic solid tumors will be enrolled in. In Part A, the safety and tolerability of C019199 will be assessed in about 25 subjects to identify the maximum tolerated dose and recommended phase Ⅱ dose (PR2D). In Part B, the safety and antitumor activity of the RP2D will be assessed in about 60 subjects in disease-specific expansion cohorts. Primary endpoints are adverse events, laboratory abnormalities, dose-limiting toxicities. Secondary endpoints will include pharmacokinetics, objective response rate, progression-free survival, and disease control rate. Exploratory biomarker analyses include CSF-1 and VEGF. Clinical trial information: CTR20202045.