A Study of GNC-077 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Inclusion criteria

• Able to understand the informed consent form, voluntarily participate in and sign the informed consent form;
• Gender is not limited;
• Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib);
• Patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors confirmed by histopathology and/or cytology who failed standard treatment;
• Must have at least one measurable lesion that meets the RECIST v1.1 definition;
• Have archived primary or recurrent tumor tissue specimens that can be submitted for central review;
• ECOG ≤1;
• The expected survival time as judged by the investigators was ≥3 months;
• Bone marrow function, renal function and liver function need to meet the requirements;
• Coagulation function: fibrinogen ≥1.5 g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN;
• Fertile female subjects or male subjects with fertile partners must use highly effective contraception from 7 days before the first dose until 12 weeks after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose;
• Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Chemotherapy, biological therapy, immunotherapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
• Patients with active infection requiring intravenous antibiotics that had not been completed more than 1 week before enrollment, with the exception of prophylactic antibiotics for puncture or biopsy;
• Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
• Toxicity from prior antineoplastic therapy is not reduced to grade I as defined in CTCAE, version 5.0;
• Patients at risk for active autoimmune disease or with a history of autoimmune disease may have central nervous system involvement;
• Pulmonary disease defined as ≥ grade 3 according to NCI-CTCAE v5.0; A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis;
• Patients with previous allogeneic hematopoietic stem cell transplantation or organ transplantation;
• Had a history of severe cardiovascular and cerebrovascular diseases;
• Patients with or with unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism within 6 months before screening;
• Brain parenchymal metastases and/or meningeal metastases or spinal cord compression, excluding stable and asymptomatic brain parenchymal metastases;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large arteries;
• Subjects with clinically significant bleeding or significant bleeding tendency within the previous 4 weeks were screened;
• Complicated with other malignant tumors within 3 years before the first administration;
• Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
• Diabetic patients with poor glycemic control;
• Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-077;
• Who had participated in a clinical trial of an unmarketed drug within 4 weeks before the trial dose;
• Had received a live vaccine within 4 weeks before the trial dose;
• Other circumstances that the investigator deemed inappropriate for participation in the trial.