Solid Tumor
Conditions
Brief summary
This study is an open-label, multicenter, non-randomized Phase I clinical study of dose-escalation and expansion to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SI-B036 bispecific antibody injection in patients with locally advanced or metastatic solid tumors.
Detailed description
The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion 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 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 solid tumors; 6. Agree to provide archived tumor tissue specimens from primary or metastatic lesions 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, 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 ≤2+ or ≤1000 mg/24h; 14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and they must be non-lactating; all enrolled patients (regardless of male or female) must adopt adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion; 15. The trial participant is capable and willing to adhere to the visit schedule, treatment plan, laboratory tests, and other study-related procedures specified in the protocol.
Exclusion criteria
1. Use of chemotherapy, biological therapy, immunotherapy, etc. within 4 weeks or 5 half-lives prior to the first dose; 2. Receipt of immunosuppressive therapy within 2 weeks prior to the first dose; 3. History of severe cardiac or cerebrovascular disease; 4. QT interval prolongation, complete left bundle branch block, etc.; 5. Active autoimmune diseases and inflammatory diseases; 6. Prior experience 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 event requiring therapeutic intervention within 6 months prior to the first dose; 9. Poorly controlled hypertension; 10. Diabetic patients with poorly controlled blood glucose; 11. History of ILD requiring steroid therapy, or current ILD, or ≥ grade 2 radiation pneumonitis; 12. Concomitant pulmonary disease causing severe respiratory impairment; 13. Active central nervous system metastases; 14. History of allergy to recombinant humanized or human-mouse chimeric antibodies, or hypersensitivity 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 dose of study drug; 18. Presence of pleural, abdominal, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first dose of study drug; 19. Imaging findings indicating tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart; 20. Study participants with clinically significant bleeding or a clear bleeding tendency within 4 weeks prior to screening; 21. History of fistula, gastrointestinal perforation, or intra-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 enrollment 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. |
| 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. |
| 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 \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| 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. |
| 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed