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

Official title

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

Overview

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.

Detailed description

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

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Harbin Medical University Cancer Hospital — Harbin

Identifiers

NCT: NCT07678970 · SI-B036-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗