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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Phase Ia: Dose limiting toxicity (DLT)
Study Overview
Brief Summary
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
SI-B036
Participants receive SI-B036 for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Intervention: SI-B036 (Drug)
Outcomes
Primary Outcomes
Phase Ia: Dose limiting toxicity (DLT)
Time Frame: Up to 21 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
Time Frame: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Phase Ib: Recommended Phase II Dose (RP2D)
Time Frame: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B036.
Secondary Outcomes
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ia: Progression-free survival (PFS)(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)