A Study of SI-B036 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SI-B036 Bispecific Antibody Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

This study is an open-label, multicenter, non-randomized Phase I clinical study with dose-escalation and expansion cohorts, designed to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of SI-B036 bispecific antibody injection in patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors.

The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion cohort phase (Phase Ib).

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to follow the protocol requirements;
2. No gender restriction;
3. Age: ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Locally advanced or metastatic digestive tract tumors and other solid tumors;
6. Agree to provide archived tumor tissue specimens within 2 years from the primary or metastatic lesion, or fresh tissue samples;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
9. Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
10. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
11. Organ function levels must meet the protocol requirements;
12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × upper limit of normal (ULN);
13. Urine protein ≤2+ or ≤1000 mg/24 h;
14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with a negative serum pregnancy result, and they must not be breastfeeding; all enrolled patients (regardless of male or female) should use adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion;
15. Trial participants are capable of and willing to comply with the visit schedules, treatment plans, laboratory tests, and other study-related procedures as stipulated in the study protocol.

Exclusion Criteria:

1. Use of chemotherapy, biotherapy, immunotherapy, etc. within 4 weeks or 5 half-lives prior to the first dose;
2. Receipt of immunosuppressive medications within 2 weeks prior to the first dose;
3. History of severe cardiac or cerebrovascular disease;
4. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
5. Active autoimmune diseases and inflammatory diseases;
6. Prior history of ≥ Grade 3 toxicity related to anti-angiogenic therapy during previous anti-angiogenic treatment;
7. Diagnosis of another solid tumor within 5 years prior to the first dose;
8. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
9. Uncontrolled hypertension;
10. Diabetic patients with poorly controlled blood glucose;
11. History of interstitial lung disease (ILD) requiring steroid therapy, or current ILD, or ≥ Grade 2 radiation pneumonitis;
12. Concurrent pulmonary disease resulting in severe impairment of respiratory function;
13. Patients with active central nervous system (CNS) metastases;
14. History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of SI-B036;
15. Prior history of organ transplantation or allogeneic hematopoietic stem cell transplantation;
16. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
17. Active infection requiring systemic therapy within 4 weeks prior to the first study drug administration;
18. Presence of pleural, abdominal, or pelvic effusion or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first study drug administration;
19. Imaging findings indicating that the tumor has invaded or encased the major thoracic blood vessels;
20. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to screening;
21. History of fistula, gastrointestinal perforation, or abdominal abscess within 6 months prior to the first dose;
22. Use of another investigational drug within 4 weeks or 5 half-lives prior to the first dose;
23. Pregnant or lactating women;
24. Other conditions deemed by the investigator to make the subject unsuitable for participation in this clinical trial.