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

Официальное название

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

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат SI-B036
  Administration by intravenous infusion for a cycle of 3 weeks.

Первичные конечные точки

• Phase Ia: Dose limiting toxicity (DLT) [Срок оценки: Up to 21 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Срок оценки: Up to 21 days after the first dose]
• Phase Ib: Recommended Phase II Dose (RP2D) [Срок оценки: Up to approximately 24 months]

Вторичные конечные точки (12)

• Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Up to approximately 24 months]
• Cmax [Срок оценки: Up to approximately 24 months]
• Tmax [Срок оценки: Up to approximately 24 months]
• T1/2 [Срок оценки: Up to approximately 24 months]
• AUC0-t [Срок оценки: Up to approximately 24 months]
• CL (Clearance) [Срок оценки: Up to approximately 24 months]
• Ctrough [Срок оценки: Up to approximately 24 months]
• ADA (anti-drug antibody) [Срок оценки: Up to approximately 24 months]
• Objective Response Rate (ORR) [Срок оценки: Up to approximately 24 months]
• Phase Ia: Progression-free survival (PFS) [Срок оценки: Up to approximately 24 months]
• Phase Ib: Disease Control Rate (DCR) [Срок оценки: Up to approximately 24 months]
• Phase Ib: Duration of Response (DOR) [Срок оценки: Up to approximately 24 months]

Критерии участия

Критерии включения

• Voluntarily sign the informed consent form and agree to follow the protocol requirements;
• No gender restriction;
• Age: ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Locally advanced or metastatic digestive tract tumors and other solid tumors;
• Agree to provide archived tumor tissue specimens within 2 years from the primary or metastatic lesion, or fresh tissue samples;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
• Organ function levels must meet the protocol requirements;
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × upper limit of normal (ULN);
• Urine protein ≤2+ or ≤1000 mg/24 h;
• 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;
• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Harbin Medical University Cancer Hospital — Харбин

Идентификаторы

NCT: NCT07678970 · SI-B036-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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