The Efficacy and Safety of IBI363 in Solid Tumors

Inclusion Criteria:

• Sign written informed consent before implementing any trial-related procedures

• Age ≥18 years old and ≤75 years old;

• No limit on the gender;

• Phase Ia: Enrollment priority is given to subjects with advanced non-small cell lungcancer and melanoma.

• Phase Ib: This study comprises seven cohorts, including:

• Cohort A: Patients with histopathologically confirmed advanced melanoma, who havefailed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.

• Cohort B: Patients with histopathologically confirmed advanced NSCLC, who havefailed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.

• Cohort C: Patients with histopathologically confirmed advanced NSCLC, who havefailed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment wasdisease stabilization for less than 6 months or disease progression.

• Cohort D: Patients with histopathologically confirmed advanced NSCLC, who havefailed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment waspartial response or complete response lasting more than 6 months.

• Cohort E: Patients with histologically confirmed advanced NSCLC, who have undergoneNGS testing confirming the presence of an ALK fusion mutation and have previouslyfailed standard treatment.

• Cohort F: Patients with histological or cytological confirmation of advanced NSCLCwho harboring EGFR mutation and failed standard treatment.

• Cohort G: Patients with histological or cytological confirmation of advanced NSCLCand failed standard treatment with rare mutations, including but not limited toROS1, BRAF V600E, METex14 skipping, HER2, NTRK, and RET fusion.

• Tumor assessment according to RECIST v1.1, at least one measurable lesion.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Known history of seizures, active central nervous system metastasis, spinalcord compression, carcinomatous meningitis, history of meningeal metastasis,and newly diagnosed brain metastasis or meningeal metastasis.

• a) Subjects who have previously received treatment for central nervous systemmetastases must meet all of the following criteria to be eligible for this study:

• Completed treatment for central nervous system metastases (e.g., whole-brainradiation therapy, stereotactic radiosurgery, or equivalent treatment) at least 14days before the first dose of the investigational drug.

• Post-treatment repeat imaging confirmed no evidence of new brain metastases orenlargement of existing brain metastatic lesions (with an interval of ≥4 weeks andusing the same imaging technique as the pre-treatment head imaging).

• No requirement for steroid treatment and stable symptoms for at least 14 days beforethe first dose of the investigational drug. b) Subjects who have not previously received treatment for central nervous systemmetastases must meet all of the following criteria to be eligible for this study:

• No symptoms related to central nervous system metastases.

• Investigator assessment that immediate treatment for central nervous systemmetastases is not required.

• A maximum of three central nervous system metastatic lesions, with each lesionhaving a maximum diameter of ≤5 mm.

2. Significant cardiovascular and cerebrovascular diseases, including:

3. Requiring medical intervention due to ventricular arrhythmias or otheruncontrolled arrhythmias, such as treatment with anti-arrhythmic drugs.

4. Severe conduction disturbances (e.g., third-degree atrioventricular block).

5. HR-corrected QT interval (QTc interval, calculated using the Fridericia method) ≥480 ms.

6. Uncontrolled hypertension (systolic blood pressure >140 mmHg and/or diastolicblood pressure >90 mmHg), a history of hypertensive crisis, or hypertensiveencephalopathy.

7. A history of myocarditis.

8. Symptomatic congestive heart failure (New York Heart Association functionalclasses II-IV) or cardiac ultrasound findings indicating left ventricularejection fraction (LVEF) <50%.

9. Any arterial thrombosis, embolism, or ischemic event (e.g., myocardialinfarction, unstable angina, cerebrovascular accident) within 6 months prior tothe first dose of the investigational drug.

10. History of deep venous thrombosis or any other serious thromboembolic eventwithin the 3 months before enrollment (implantable venous access port orcatheter-related thrombosis, or superficial venous thrombosis are notconsidered "serious" thromboembolic events).