The study is a prospective multi-cohort clinical study. The study is divided into two phases, Phase Ia and Phase Ib. In Phase Ia, a dose escalation portion was conducted using a 3+3 dose-escalation design, with a preference for enrolling subjects with advanced non-small cell lung cancer and melanoma. Phase Ib represents the cohort expansion phase, comprising seven cohorts.

The study is a prospective multi-cohort clinical study. The study is divided into two phases, Phase Ia and Phase Ib. In Phase Ia, a dose escalation portion was conducted using a 3+3 dose-escalation design, with a preference for enrolling subjects with advanced non-small cell lung cancer and melanoma. Phase Ib represents the cohort expansion phase, comprising seven cohorts. All the research data were collected follow the SAP.

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 lung cancer and melanoma.
• Phase Ib: This study comprises seven cohorts, including:
• Cohort A: Patients with histopathologically confirmed advanced melanoma, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.
• Cohort B: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment and CD73 ≥++ confirmed by IHC.
• Cohort C: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was disease stabilization for less than 6 months or disease progression.
• Cohort D: Patients with histopathologically confirmed advanced NSCLC, who have failed PD-1/PD-L1 treatment, and whose best response during PD-1/PD-L1 treatment was partial response or complete response lasting more than 6 months.
• Cohort E: Patients with histologically confirmed advanced NSCLC, who have undergone NGS testing confirming the presence of an ALK fusion mutation and have previously failed standard treatment.
• Cohort F: Patients with histological or cytological confirmation of advanced NSCLC who harboring EGFR mutation and failed standard treatment.
• Cohort G: Patients with histological or cytological confirmation of advanced NSCLC and failed standard treatment with rare mutations, including but not limited to ROS1, 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, spinal cord 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 system metastases must meet all of the following criteria to be eligible for this study:

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

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

• No requirement for steroid treatment and stable symptoms for at least 14 days before the first dose of the investigational drug.

  b) Subjects who have not previously received treatment for central nervous system metastases 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 system metastases is not required.

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

• 2. Significant cardiovascular and cerebrovascular diseases, including:

  1. Requiring medical intervention due to ventricular arrhythmias or other uncontrolled arrhythmias, such as treatment with anti-arrhythmic drugs.
  2. Severe conduction disturbances (e.g., third-degree atrioventricular block).
  3. HR-corrected QT interval (QTc interval, calculated using the Fridericia method) ≥480 ms.
  4. Uncontrolled hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy.
  5. A history of myocarditis.
  6. Symptomatic congestive heart failure (New York Heart Association functional classes II-IV) or cardiac ultrasound findings indicating left ventricular ejection fraction (LVEF) <50%.
  7. Any arterial thrombosis, embolism, or ischemic event (e.g., myocardial infarction, unstable angina, cerebrovascular accident) within 6 months prior to the first dose of the investigational drug.
  8. History of deep venous thrombosis or any other serious thromboembolic event within the 3 months before enrollment (implantable venous access port or catheter-related thrombosis, or superficial venous thrombosis are not considered "serious" thromboembolic events).