Clinical Studies for the Treatment of Advanced Solid Tumors

Inclusion Criteria:

1. Be at least 18 years old.

2. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1.

3. At least 1 measurable lesion as determined by RECIST v1.1 assessment. Positronemission tomography (PET) scans and ultrasonography cannot be used for diagnosticpurposes.

4. All acute toxicities due to prior antineoplastic therapy or surgery have resolved toGrade 0-1 (according to NCI-CTCAE v5.0) or to the level specified by theenrollment/exclusion criteria. Other toxicities that, in the opinion of theinvestigator, do not pose a safety risk to the participant, such as alopecia,fatigue, and hearing loss, are excluded.

5. Have adequate organ and bone marrow function, defined below:

6. Routine blood tests: (no transfusion, no granulocyte colony-stimulating factor (G-CSF), no drug correction) white blood cell count (WBC) ≥ 3,000/mm3 (3.0 × 109/L), neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 109/L), platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L), hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L);

7. Biochemical tests: serum albumin ≥ 3.0 g/dL (30 g/L), serum creatinine ≤ 1.5times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (calculated using the Cockcroft-Gault formula), total bilirubin (BIL) ≤ 1.5times the upper limit of normal (ULN); Aspartate aminotransferase (AST/SGOT)and alanine aminotransferase (ALT/SGPT) levels ≤ 2.5 times the upper limit ofnormal (ULN), and patients with liver metastases should ≤ 5× ULN;

8. The international normalized ratio (INR) is ≤ 1.5, and the prothrombin time (PT) and activated partial thromboplastin time (APTT) are ≤ 1.5 times ULN;

9. Urine protein< 2+; If the urine protein ≥ 2+, the 24-hour urine proteinquantification shows that the protein must be ≤ 1 g;

10. Cardiac function: left ventricular ejection fraction ≥ 50% on echocardiography.

11. Expected survival ≥ 12 weeks;

12. Non-childbearing is defined as a woman who has reached a postmenopausal state, orwho has had a medically documented bilateral oophorectomy. Male participants andfemale participants of childbearing potential must agree to use 1 medically approvedform of contraception for the duration of the trial and for 6 months after the lastdose of the trial drug or 9 months after the last dose of the chemotherapy drug (oxaliplatin), whichever is later, and a negative serum pregnancy test within 3 daysprior to starting the study drug and not lactating.

13. With the consent of the person and has signed the informed consent form, willing andable to comply with the planned visits, study treatment, laboratory tests, and othertrial procedures. Enrollment criteria applicable to each cohort: Cohorts A1 and A2 must meet the following enrollment criteria:

14. Patients with a pathologically confirmed diagnosis of Gastric cancer (GC) orGastroesophageal junction cancer (GEJC), evidence of unresectable advanced ormetastatic disease, and histologic confirmation of adenocarcinoma.

15. Provide negative reports of human epidermal growth factor receptor 2 (HER2)overexpression or amplification; HER2 overexpression or amplification negative isdefined as Immunohistochemistry (IHC) 0/1+, or IHC 2+ with Fluorescence In SituHybridization (FISH)/In Situ Hybridization (ISH) negative.

16. No prior systemic therapy (including anti-HER-2 therapy) for advanced or metastaticGC/GEJC. Patients who have received prior adjuvant or neoadjuvant therapy forGC/GEJC (including: chemotherapy, radiotherapy, or chemoradiotherapy) have a time offirst recurrence or disease progression greater than 6 months from the end of thelast treatment. Participants who have previously received anti-tumor traditionalChinese medicine preparations are allowed, but must be discontinued at least 14 daysprior to enrollment.

17. Participants should provide tumor tissue samples: fresh specimens (preferred) orformalin-fixed, paraffin-embedded tumor tissue, or microneedle aspiration tissuecollected at radiotherapy-naïve sites within approximately 24 months prior toenrollment (specimens within 6 months prior to the first dose of study drug arerecommended and no systemic therapy has been received since the sample wasobtained). For participants who are unable to provide tissue samples but meet otherenrollment conditions, the investigator and the sponsor will jointly decide whetherto enroll. Cohorts A3 and A4 need to meet the following enrollment criteria:

18. Patients with pathologically confirmed solid tumors with evidence of advanced ormetastatic unresectable disease.

19. Patients with advanced or metastatic solid tumors who have failed at least one priorline of standard therapy. Participants who have previously received anti-tumortraditional Chinese medicine preparations are allowed, but must be discontinued atleast 14 days prior to enrollment.

Exclusion Criteria:

1. Microsatellite Instability-High (MSI-H)/deficient Mismatch Repair (dMMR) is known.

2. Presence of uncontrolled or symptomatic active central nervous system metastasesthat can manifest as the presence of clinical symptoms, cerebral edema, spinal cordcompression, carcinomatous meningitis, leptomeningeal disease, and/or progressivegrowth. Central Nervous System (CNS) metastases may be enrolled in the study if theyhave been adequately treated (surgical or radiographed) and neurological symptomshave returned to baseline (except for residual signs or symptoms associated with CNStreatment) by at least 14 days prior to enrollment.

3. Pleural effusion and ascites that cannot be controlled after puncture and drainageand other treatments within 14 days prior to enrollment; Pericardial effusion withclinical symptoms or moderate or above.

4. Participant weight loss of more than 20% in 2 months prior to enrollment.

5. Participant weight loss of more than 20% in 2 months prior to enrollment:

6. Received Chemokine receptor 8 (CCR8) antibody, CytotoxicT-lymphocyte-Associated Protein-4 (CTLA-4) antibody, or other drugs that act onTreg before enrollment.

7. Major surgery within 28 days prior to enrollment (tissue biopsy andperipherally venipuncture central venous catheter placement [PeripherallyInserted Central Venous Catheters (PICC)]/port implantation required fordiagnosis are permitted).

8. Use of immunosuppressive medications, excluding nasal spray and inhaledcorticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg/d prednisone or equivalent pharmacophysiological doses of othercorticosteroids) within 14 days prior to enrollment.

9. Live attenuated vaccine within 28 days prior to enrollment or plannedadministration during the study and within 60 days after the end of study drugtreatment.

10. Received anti-tumor therapy (including chemotherapy, radiotherapy,immunotherapy, endocrine therapy, targeted therapy, biological therapy, ortumor embolization) within 28 days prior to enrollment.

11. Diagnosis of any other malignancy within 5 years prior to enrollment, except forbasal cell carcinoma or squamous cell carcinoma of the skin that can be treatedlocally and has a clear medical record documented as cured, except for basal cellcarcinoma or squamous cell carcinoma of the skin, superficial bladder cancer,carcinoma in situ of the cervix, intraductal carcinoma in situ of the breast, andpapillary carcinoma of the thyroid gland.

12. Presence of any active, known or suspected autoimmune disease. Participants who arein a stable state and do not require systemic immunosuppressive therapy, such as:type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy,and skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, andalopecia) are allowed.

13. Significant clinically significant bleeding symptoms or definite bleeding tendencywithin 3 months prior to enrollment; Arterial/venous thrombotic events occurredwithin 6 months prior to enrollment, such as cerebrovascular accident (includingtransient ischemic attack, cerebral hemorrhage, cerebral infarction), deep veinthrombosis and pulmonary embolism.

14. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair orrecent peripheral arterial thrombosis) within 6 months prior to enrollment.

15. Severe, non-healing, or dehiscence wounds and active ulcers or untreated fractures.

16. Presence of grade >1 peripheral neuropathy.

17. Gastrointestinal perforation and/or gastrointestinal fistula within 6 months priorto enrollment;

18. Previous intestinal obstruction and/or clinical signs or symptoms ofgastrointestinal obstruction within 6 months prior to enrollment, includingincomplete obstruction related to a pre-existing condition or requiring routineparenteral hydration, parenteral nutrition, or tube feeding: Patients may be allowedto be enrolled in the study if at the time of initial diagnosis if the patient hasreceived definitive (surgical) treatment to resolve symptoms.

19. Presence of interstitial lung disease, non-infectious pneumonitis, or uncontrolledsystemic disease (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia,etc.).

20. Known hypersensitivity to the study drug or any of its excipients; or have had asevere allergic reaction to other monoclonal antibodies.

21. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiencysyndrome (AIDS), untreated active hepatitis (hepatitis B, defined as Hepatitis BVirus (HBV)-DNA ≥ 500 IU/ml; Hepatitis C, defined as Hepatitis C Virus (HCV)-RNAabove the lower limit of detection of the analytical method) or co-infection withhepatitis B and C.

22. Presence of cardiac clinical symptoms or disease that is not well controlled:

23. Cardiac insufficiency of grade 2 and above according to the New York HeartAssociation (NYHA) criteria.

24. Corrected QT Interval (QTc) > 480 ms; The QTc interval was calculated using theFridericia formula.

25. Severe/unstable angina.

26. Myocardial infarction occurred within 12 months prior to enrollment.

27. Clinically significant supraventricular or ventricular arrhythmias andsymptomatic congestive heart failure.

28. Systemic antibiotic use within 28 days prior to enrollment for ≥ 7 days, orunexplained fever >38.5°C during screening/before the first dose (as judged by theinvestigator, fever due to tumor causes can be enrolled).

29. Known history of allogeneic organ transplantation or allogeneic hematopoietic stemcell transplantation.

30. Participation in any other drug clinical study within 4 weeks prior to enrollment,or no more than 5 half-lives from the last study drug.

31. Known history of psychotropic substance abuse or drug abuse.

32. Presence of other serious physical or psychiatric illnesses or laboratoryabnormalities that may increase the risk of participating in the study, or interferewith the results of the study, and patients who, in the opinion of the investigator,are not suitable to participate in this study.