A Study of GH21 Combined With Previous Target Therapy or Immunotherapy in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Subjects or their legal representatives can understand and voluntarily sign thewritten ICF (before the start of screening and any study procedures);

2. Male or female subjects aged ≥18 years;

3. Patients with advanced solid tumors confirmed by cytological or histologicalassessments;

4. Patients have at least one measurable lesion as defined by RECIST v1.1 (a tumorlesion in the area that has undergone radiotherapy or other loco-regional therapies,is generally not considered as measurable unless there is a disease progression inthe lesion);

5. Life expectancy of ≥ 3 months;

6. ECOG PS score of 0-1;

7. The subjects must have adequate organ functions;

8. Male and female of reproductive potential must agree to take reliable contraceptivemeasures (hormone or barrier methods or abstinence) from signing the ICF until 6months after the last dose. Pregnancy test results must be negative for female ofreproductive potential within 7 days prior to the first dose of the investigationalproduct.

Exclusion Criteria:

1. Subjects who receive any chemotherapy or antitumor biologics within 3 weeks, orantitumor therapies such as radiotherapy and endocrine therapy within 4 weeks priorto the first dose of the investigational product, except for the following:

• Use of nitrosoureas or mitomycin C within 6 weeks prior to the first dose ofthe investigational product;

• Oral administration of fluorouracils, small molecule targeted drugs, andChinese herbal medicines or Chinese patent medicines with antitumor indicationswithin 5 half-lives or 2 weeks before the first dose of the investigationalproduct (whichever is shorter);

• Small molecule TKI inhibitors within 5 half-lives or 2 weeks prior to the firstdose of the investigational product (whichever is shorter);

• Local palliative radiotherapy within 2 weeks prior to the first dose of theinvestigational product; Note: If the latest anti-tumor therapy beforeenrollment is only the intended combination therapy, follow-up therapy can becarried out according to the original treatment cycle according to clinicalneeds, without waiting for elution.

2. Subjects who have had another investigational new drug or therapy within 4 weeksprior to the first dose of the investigational product;

3. Subjects who have had a major organ surgery (excluding needle biopsy) or significanttrauma within 4 weeks prior to the first dose of the investigational product, orrequire an elective surgery during the study;

4. Subjects who have received strong P-gp inhibitors or inducers within 2 weeks orwithin 5 half-lives prior to the first dose of the investigational product;

5. Subjects with evidence of the following heart conditions:

• Acute myocardial infarction, unstable angina pectoris, coronary artery bypassgrafting, cerebrovascular accident, or transient ischemic attack within 6months prior to the first dose of the investigational product;

• Grade III-IV heart failure diagnosed according to the cardiac functionclassification of the New York Heart Association at screening;

• Echocardiography (ECHO) shows the left ventricular ejection fraction (LVEF) ≤ 50% at screening;

• QT interval corrected by Fridericia method (QTcF) is ≥ 450 ms (male) or ≥ 470ms (female) at screening;

• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolicblood pressure ≥ 100 mmHg) despite of medication treatment at screening;

6. Subjects with dysphagia, gastrointestinal disorders that affect drug absorption, orother malabsorption conditions, such as intestinal obstruction, Crohn's disease,ulcerative colitis, short bowel syndrome, delayed gastric emptying, or severegastrointestinal toxicities that have not resolved to Grade 2 or lower prior to thefirst dose of the investigational product; or subjects are diagnosed with aclinically significant or acute gastrointestinal disease;

7. Subjects with Uncontrolled pleural effusion, pericardial effusion, or pleuraleffusion requiring repeated drainage (once a month or more frequently);

8. Subjects with active central nervous system metastasis and/or carcinomatousmeningitis (e.g., brain metastases accompanied by central nervous system symptoms,including headache, vomiting and dizziness, etc.);

9. Subjects with interstitial pneumonia, or any evidence of clinically activeinterstitial lung disease within 6 months before the first dose of theinvestigational product;

10. Sujects with arteriovenous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks), venous thrombosis, and pulmonary embolism,occurred within 6 months before the first dose of the investigational product;

11. Subjects with a history of other malignancies (excluding those deemed eligible bythe investigator, such as skin squamous cell carcinoma in situ, basal cellcarcinoma, and cervical cancer in situ that have been cured and have not relapsedfor 5 years);

12. Subjects with a history of severe allergies, a history of allergies to theinvestigational drug/any excipient/combination drug, or to multiple drugs;

13. Subjects with hepatitis B virus infection (HBsAg positivity and DNA copies < 100IU/mL); or hepatitis C virus infection (HCV antibody positivity, and HCV RNA > ULN);or human immunodeficiency virus infection (HIV antibody positivity); or infectedwith treponema pallidum (defined as TP-Ab positive);

14. Subjects with active infections requiring anti-infective treatment (Grade ≥ 2) orfever > 38°C of unknown etiology within 28 days prior to the first dose of theinvestigational product;

15. Subjects with autoimmune diseases in the active phase within 28 days prior to thefirst dose of the investigational product;

16. Subjects with any toxicity caused by a previous antitumor therapy that has notresolved to Grade ≤ 1 according to CTCAE 5.0 (except for alopecia, Grade 2peripheral neuropathy, and/or other Grade ≤ 2 AEs of insignificant safety risks)before the first dose of the investigational product;

17. Female subjects who are pregnant or breastfeeding;

18. Subjects who are not suitable for this study due to any clinical or laboratoryabnormalities or other reasons as assessed by the investigator.