A Study of SI-B036 in Patients With Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors
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 Breast Cancer and Other Solid Tumors
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Sa Xiao, PHD
- Phone Number: +8615013238943
- Email: xiaosa@baili-pharm.com
Study Locations
-
-
Beijing Municipality
-
Beijing, Beijing Municipality, China
- Recruiting
- Cancer Hospital Chinese Academy of Medical Sciences
-
Contact:
- Binghe Xu
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Voluntarily sign the informed consent form and comply with the protocol requirements;
- No gender restriction;
- Age: ≥18 years and ≤75 years;
- Expected survival time ≥3 months;
- Locally advanced or metastatic breast cancer and other solid tumors;
- Agree to provide archived tumor tissue specimens from the primary or metastatic site within 2 years, 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 antitumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
- Organ function levels must meet the required criteria;
- Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5 × upper limit of normal;
- Urine protein ≤1+ 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 be non-lactating; all enrolled patients (both males and females) must adopt adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion;
- The trial participant must be able and willing to comply with the protocol-specified visits, treatment plan, laboratory tests, and other study-related procedures.
Exclusion Criteria:
- Use of chemotherapy, biotherapy, immunotherapy, or similar treatments within 4 weeks or 5 half-lives prior to the first dose;
- Receipt of immunosuppressive drug therapy 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 experience 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;
- Poorly controlled hypertension;
- Diabetes mellitus with poor glycemic control;
- 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;
- Active central nervous system metastases;
- History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of SI-B036;
- Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Positive for human immunodeficiency virus 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 dose of the study drug;
- Presence of pleural, abdominal, or pelvic effusion, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first dose of the study drug;
- Imaging findings suggesting tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart;
- Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to screening;
- History of fistula, gastrointestinal perforation, or intra-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 breastfeeding women;
- Other conditions deemed by the investigator to make the participant unsuitable for participation in this clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: 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.
|
Administration by intravenous infusion for a cycle of 3 weeks.
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Up to 21 days after the first dose
|
|
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.
|
Up to 21 days after the first dose
|
|
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.
|
Up to approximately 24 months
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
AUC0-t
Time Frame: 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.
|
Up to approximately 24 months
|
|
Objective Response Rate (ORR)
Time Frame: Up to approximately 24 months
|
Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).
|
Up to approximately 24 months
|
|
Disease Control Rate (DCR)
Time Frame: Up to approximately 24 months
|
Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.
|
Up to approximately 24 months
|
|
Duration of Response (DOR)
Time Frame: Up to approximately 24 months
|
Duration of Response (DOR) is defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.
|
Up to approximately 24 months
|
|
Treatment-Emergent Adverse Event (TEAE)
Time Frame: 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.
|
Up to approximately 24 months
|
|
Cmax
Time Frame: Up to approximately 24 months
|
Cmax is defined as the maximum observed drug concentration in plasma after administration.
|
Up to approximately 24 months
|
|
Tmax
Time Frame: Up to approximately 24 months
|
Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration.
|
Up to approximately 24 months
|
|
T1/2
Time Frame: Up to approximately 24 months
|
T1/2 is defined as the time required for the plasma concentration of a drug to decrease by 50% during the elimination phase.
|
Up to approximately 24 months
|
|
CL (Clearance)
Time Frame: Up to approximately 24 months
|
Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time.
|
Up to approximately 24 months
|
|
Ctrough
Time Frame: Up to approximately 24 months
|
Ctrough is defined as the lowest serum concentration prior to the next dose will be administered.
|
Up to approximately 24 months
|
|
Progression-free Survival (PFS)
Time Frame: 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.
|
Up to approximately 24 months
|
|
Anti-drug Antibody (ADA)
Time Frame: Up to approximately 24 months
|
Frequency of anti-SI-B036 antibody (ADA) will be investigated.
|
Up to approximately 24 months
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- SI-B036-103
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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