A Phase II Study of SHR-4602 as Montherapy or in Combination With Other Anti-tumor Therapies in Advanced Solid Tumors

Inclusion criteria

• 18-80 years old;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Stage I: subjects with pathologically confirmed locally advanced unresectable or metastatic solid tumors, who have failed at least 1 line of standard treatment;
• Provide archived or fresh tumor tissue；HER2 expression is required for subjects in Stage I;
• At least one measurable lesion according to RECIST v1.1；
• Expected survival ≥12 weeks
• Good level of organ function；
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose, be non-lactating. Male subjects whose partners are women of childbearing age and female subjects who are fertile must agree to avoid sperm or egg donation during the treatment period until 8 months after the last dose of the investigational drug;
• Have the ability to give informed consent, have signed informed and able to comply with the treatment plan to visit the tests and other procedural requirements；

Exclusion criteria

• Inadequately treated central nervous system metastases or the presence of uncontrolled or symptomatic active central nervous system metastases；
• Subjects with peripheral neuropathy；
• Have received anti-cancer treatment within 4 weeks prior the first dose of study treatment;
• Are participating in another clinical study or have received the last dose in a clinical study less than 4 weeks from the first dose;
• Subjects who have received systemic immunosuppressant treatment within 14 days prior the first dose of study treatment;
• Have received treatment with strong CYP3A inducers or inhibitors, or P-gp inhibitors or inducers within 5 half-lives prior to the first dose;
• Toxicity and/or complications of previous antitumor therapy has not resolved to NCI-CTCAE level ≤1 or exclusion criteria；
• Have the following lung diseases or medical history: (1) known or suspected interstitial lung disease; (2) moderate to severe lung diseases that seriously affect lung function within the past 3 months; (3) any autoimmune, connective tissue, or inflammatory disease involving the lungs; (4) prior pneumonectomy; (5) Grade ≥ 3 interstitial lung disease during prior treatment with immune checkpoint inhibitors.
• Stage 2: ≥ grade 3 immune-related adverse events occurred during previous treatment with immune checkpoint inhibitors；
• Have any active, known or suspected autoimmune diseases;
• Moderate or severe ascites with clinical symptoms, uncontrolled or moderate or above pleural effusion and pericardial effusion；
• The presence of clinical cardiac symptoms or diseases that are not well controlled；
• Known hereditary or acquired hemorrhage and thrombophilia；
• Have untreated active hepatitis；
• Subjects who had a severe infection within 30 days prior to the first dose；
• Any other malignancy diagnosed within the previous 5 years；
• Patients with active tuberculosis infection within 1 year prior to enrollment, or with a history of active tuberculosis infection more than 1 year prior but without formal treatment；
• History of immune deficiency；
• Live attenuated vaccines were used within 28 days prior to initial study administration or during the expected study period；
• Known severe allergic reactions to any component of SHR-4602, or other monoclonal antibody/fusion protein drugs；
• Female subjects who are pregnant or plan to become pregnant during the study period；
• The presence of uncontrolled mental illness and other conditions known to affect the completion of the study process, such as alcohol, drug or substance abuse, and criminal detention；
• In the investigator's judgment, there are any other circumstances that may increase the risk of participating in the study, interfere with the study results, or make participation in the study inappropriate.