This is a phase 1/2, open-label, multicenter study assessing the safety, tolerability, pharmacokinetics and efficacy of GW5282 in participants with locally advanced or metastatic solid tumors. This study comprised of a dose escalation phase to determine the MTD and the RP2D and a dose expansion phase to further explore the safety, PK and efficacy of GW5282.

Inclusion Criteria:

1. All participants must provide a signed, dated written informed consent (ICF) prior to any study-specific procedures, sampling, and analysis.

2. Male and female participants must be ≥18 years of age at the time of signing the ICF.

3. Eastern Cooperative Oncology Group performance status of 0-1.

4. Histologically or cytologically confirmed locally advanced or metastatic solid tumors who has failed standard of cares (SoCs).

5. Life expectancy ≥3 months.

6. At least one measurable lesion according to RECIST 1.1.

7. Tumor tissue sample requirements: sections of formalin-fixed paraffin-embedded (FFPE) tissue from freshly obtained biopsy sample or archived tumor sample.

8. Adequate organ and marrow function.

9. Participants should be able to comply with the requirements of this study for medication use and follow-up.

10. If the female partner of a male participant has a potential for pregnancy, he must agree to use contraception (such as condoms) and refrain from donating sperm during the treatment period and for at least 6 months after the last dose of study treatment.

11. Female participants should use adequate contraception during the treatment period and for at least 3 months after the last dose of study treatment. Female participants with potential pregnancy should have a negative pregnancy test prior to the first administration of investigational drug. Female participants may also be enrolled if they meet one of the following criteria:

    • Postmenopausal women: older than 50 years and more than 12 months postmenopausal after discontinuation of all exogenous hormone therapy. Women under 50 years of age, more than 12 months postmenopausal after discontinuation of all exogenous hormone therapy, and with luteinizing hormone and follicle-stimulating hormone levels at postmenopausal levels.
    • History of irreversible hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (excluding tubal ligation)."

Exclusion Criteria:

1. Any unresolved > grade 1 (according to CTCAE version 5.0) adverse event (excluding alopecia, anemia, neutropenia, and thrombocytopenia) prior to the first administration of investigational drug.

2. Any known active central nervous system metastases and/or carcinomatous meningitis and/or spinal cord compression.

3. Having any of the following treatment history:

   • previously treated with GW5282 or other EZH pathway inhibitors.
   • previously received any cytotoxic chemotherapy, investigational drug, or other anticancer drug (excluding macromolecular drugs) or clinical trial within 7 days or 5 half-lives (whichever is longer) prior to the first administration of the investigational drug.
   • previously received any macromolecular drug (such as immunotherapy, monoclonal antibodies, bispecific antibodies, or antibody-drug conjugates) within 28 days prior to the first administration of the investigational drug.
   • Underwent major surgery (excluding vascular access surgery) or suffered severe trauma within 4 weeks prior to the first administration of the investigational drug.
   • Received limited field of radiation to alleviate symptoms within 7 days prior to the first administration of the investigational drug, or received more than 30% or extensive field of radiation to the bone marrow within 28 days prior to the first administration of the investigational drug.
   • Received live-attenuated vaccine or viral vector vaccine within 4 weeks prior to the first administration of the investigational drug."

4. Active infectious diseases.

5. History of stroke or intracranial hemorrhage within 6 months prior to the first administration of the investigational drug.

6. History of interstitial lung disease (ILD), radiation pneumonitis requiring corticosteroid therapy, or any clinically active interstitial lung disease, or immunotherapy-related pneumonitis.

7. Uncontrolled systemic disease including uncontrolled hypertension and active bleeding after investigator's assessment.

8. Judgment by the investigator that the participant is unlikely to comply with the study procedures, restrictions, and requirements.