Gastrointestinal Tumor, Solid Tumor
Conditions
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).
Interventions
DRUGSI-B036
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | 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) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of SI-B036. The type, frequency and severity of TEAE will be evaluated during the treatment of SI-B036. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of SI-B036 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of SI-B036 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of SI-B036 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of SI-B036 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of SI-B036 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-SI-B036 antibody (ADA) will be investigated. |
| Phase Ia: Progression-free survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
| Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1. |
| Phase Ib: Disease Control Rate (DCR) | Up to approximately 24 months | The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| Phase Ib: Duration of Response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed