This is a first-in-human, multicenter, open-label, phase I/Ⅱa clinical study of HMPL-A580 in participants with unresectable, advanced or metastatic solid tumors.

To evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of HMPL-A580 in solid tumors.

To characterize the safety, tolerability, and preliminary efficacy of HMPL-A580 at RDE(s) to determine recommended dose(s) for phase 2 dose (RP2D) or phase 3 dose (RP3D) in participants with selected solid tumors.

Inclusion Criteria:

1. Understood this study and are able to voluntarily sign the informed consent form (ICF);
2. Male or Female, Age ≥ 18 years;
3. Histological confirmed, unresectable, advanced or metastatic solid tumor
4. Participants must have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
5. Life expectancy ≥ 12 weeks
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

Exclusion Criteria:

1. An established diagnosis of type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus
2. Use strong inhibitors of cytochrome P450 3A4 enzyme (CYP3A4), and inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) within 5 elimination half-lives or 2 weeks (whichever is longer) before the first dose of study drug
3. Major surgery within 28 days prior to the first dose of study drug
4. Active infection requiring systemic treatment
5. Participant has received a live within 3 months before study enrollment
6. History of inflammatory gastrointestinal diseases
7. Known hypersensitivity to any component of HMPL-A580
8. Pregnant (positive pregnancy test) or lactating;