This study is an investigation to evaluate the safety/tolerability, pharmacokinetics (PK), and efficacy of GFH276 as a single agent in patients with advanced solid tumors harboring RAS mutations.

The primary objectives of the Phase I study are to assess the safety/tolerability, PK, and preliminary efficacy of GFH276 in patients with advanced solid tumors harboring RAS mutations, and to determine the Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of GFH276.

The primary objective of the Phase II study is to evaluate the efficacy of GFH276 in patients with RAS-mutant advanced pancreatic ductal adenocarcinoma (PDAC), advanced non-small cell lung cancer (NSCLC), advanced colorectal cancer (CRC), and other advanced solid tumors.

Inclusion Criteria:

1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
2. Male or female ≥ 18 years old and ≤75 years old.
3. ECOG performance status of 0-1.
4. With a life expectancy of ≥3 moths
5. Have at least one measurable lesion according to RECIST1.1, and the phase Ia allows no measurable lesion.
6. Adequate laboratory parameters during the screening period.

Exclusion Criteria:

1. Active brain metastases.
2. Prior treatment with a PAN-RAS inhibitor.
3. Palliative radiotherapy was completed within 14 days before the first dose.
4. Have poorly controlled or severe cardiovascular disease.
5. Subjects with active hepatitis B or active hepatitis C.
6. Known allergy to the study drug or its components.
7. Pregnant or lactating women.