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

This study is an open-label, multicenter, dose-escalation and expansion, non-randomized 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 gynecological 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 comply with 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 gynecological tumors and other solid tumors;
6. Agree to provide archived tumor tissue specimens from the primary or metastatic site within 2 years, or fresh tissue samples;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. ECOG performance status score of 0 or 1;
9. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
10. No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
11. Organ function levels must meet the requirements;
12. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5 × ULN;
13. Urine protein ≤1+ or ≤1000 mg/24h;
14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test being negative, and they must not be lactating; all enrolled patients (regardless of male or female) must use adequate barrier contraception throughout the entire treatment period and for 6 months after treatment completion;
15. Trial participants must be able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the protocol.

Exclusion Criteria:

1. Use of chemotherapy, biological therapy, immunotherapy, or other treatments within 4 weeks or 5 half-lives prior to the first dose;
2. Receipt of immunosuppressive drug therapy 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 occurrence of ≥ Grade 3 toxicity related to anti-angiogenic therapy when receiving such therapy previously;
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. Poorly controlled hypertension;
10. Diabetes mellitus with poor glycemic control;
11. History of interstitial lung disease requiring corticosteroid therapy, or currently having ILD, or ≥ Grade 2 radiation pneumonitis;
12. Concurrent pulmonary disease resulting in severe respiratory impairment;
13. Active central nervous system 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 organ transplantation or allogeneic hematopoietic stem cell transplantation;
16. Positive for human immunodeficiency virus antibody, 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. Pleural, abdominal, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first study drug administration;
19. Imaging findings indicating tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart;
20. Trial participants with clinically significant bleeding or significant 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 breastfeeding women;
24. Other conditions deemed by the investigator to make the participant unsuitable for participation in this clinical trial.