A Phase Ⅰa Clinical Study Exploring Efficacy of SIBP-03 When Treating the Patients With Advanced Malignant Solid Tumors.

The inclusion criteria:

• Male and female aged between 18 and 75 years old.
• The enrolled subjects shall conform to the following criteria (Dose Escalation phase):Histologically or cytologically confirmed locally advanced or metastatic solid tumoursresistant or refractory to conventional treatment, for which no conventional therapyexists or is not considered appropriate by the Investigator. (Priority for inclusionbut not limited to head and neck squamous cell carcinoma, esophageal squamous cellcarcinoma and breast cancer with high HER2 expression).
• The enrolled subjects shall conform to the following criteria (Joint extension phase):Cohort 1: Patients in recurrent/metastatic advanced head and neck squamous cellcarcinoma (HNSCC) who is histologically or cytologically confirmed. The patient isalso unsuitable for radical surgical resection, failed from standard treatment, orpreviously treated by PD-1 mAb therapy (unless patient is not suitable for PD-1therapy). Cohort 2: Patients in advanced breast cancer (BC) with her2-overexpressionwho is histopathologically or cytologically confirmed, previously untreated withanti-HER2-targeted therapy such as trastuzumab or eligible for re-use though once beentreated with trastuzumab.
• At least one targeted lesion that is measurable (according to RECIST V1.1 criteria, CTor MRI) and that lesion has not received radiation therapy.
• ECOG fitness score is between 0 and 1.
• Life expectancy of at least 3 mouths.
• Adequate organ function（No blood transfusion, granulocyte colony-stimulating factor (G-CSF injection, or other medical support within 14 days prior to the use of theinvestigational drug)
• The blood pregnancy test for women of reproductive age was negative during thescreening period, and subjects of reproductive age (including male subjects) have nopregnancy plan and shall voluntarily use effective contraception during the trial and 6 months after the last dose.
• Voluntarily participate in this study and provide written informed consent.

The exclusion criteria:

• Subjects with the following tumors: Malignancy other than the tumor treated in thisstudy during the past 5 years (except for thyroid cancer, cured basal cell carcinomaof the skin, and carcinoma in situ of the cervix). Untreated central nervous system (CNS) primary tumors or metastases. Meningeal metastatic carcinoma. Patients with BMSwho had previously received systemic and radical BMS treatment (radiotherapy orsurgery), and who had been stable without any clinical symptoms for at least 4 weekswith systemic hormone therapy been stopped for more than 2 weeks.
• Subjects who have any of the following treatment history or surgical history, or whoplan to receive any of the following antitumor treatments during the trial period：Patients who received proprietary Chinese medicines whose specifications explicitlyincluded antitumor effects within 2 weeks prior to the first dose. Patients undergoingmaintenance therapy within 6 months after surgery. Patients who have not recovered tonormal or ≤level 1 toxicity from previous treatment (except for hair loss). Patientswho received major surgery, radiation, biotherapy, or chemotherapy within 4 weeksprior to initial dose, or who were systematically treated by other investigationalagents with unhealed surgical wounds, ulcers or fractures. Patients scheduled toreceive any other antitumor therapy during the trial period should be excluded (exceptfor testosterone reduction therapy in prostate cancer patients). Patients receivedimmunosuppressants or any systemic corticosteroids within 1 week prior to the firstdose. Patients previously treated with anti-HER3 drug.
• The subject's past medical history or laboratory examination shows any of thefollowing abnormalities: Abnormal coagulation function with bleeding tendency orreceiving thrombolytic or anticoagulant therapy or with blood loss/donation of morethan 200 mL within 2 months prior to drug administration. A history ofimmunodeficiency, including positive HIV, or other acquired or congenitalimmunodeficiency disease, or a history of organ transplantation. A past history ofneurological or psychiatric disorders, including epilepsy or dementia.
• Patients with positive TP test during screening period; with active HBV、HCV infection;except for stable hepatitis B infection by drug therapy (DNA titer not higher than 500IU/mL or copy number <1000 copies/mL) and cured hepatitis C infection(negative HCV RNAtest).
• Ascites, pleural effusion and pericardial effusion with clinical symptoms during thescreening period, or patients requiring drainage or previously drained within 4 weeksprior to initial dose.
• Concommitted with a serious, progressive, or uncontrolled illness, assessed by theinvestigator to increase the risk of study participation during the screening period,including but not limited to: Cerebrovascular accident or transient ischemic attack (within 6 months prior to screening). Heart disease judged by the investigator to beunsuitable for the study, abnormal cardiac function or renal function withseverity≥grade II.
• Concomitant diseases (e.g. severe hypertension, diabetes, thyroid disease, activeinfection, etc.) that seriously endanger patients' safety or affect patients' abilityto complete the study, according to the investigator's judgment.
• Have a history of severe allergy, or allergic to protein products, CHO cell products,other recombinant human or humanized antibodies or components of the investigationaldrug.
• Female who is pregnant or lactating.
• Patients deemed unsuitable for inclusion by the investigator.