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

Overview

This study is an open-label, multicenter, dose-escalation and expansion, non-randomized Phase I clinical study evaluating 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.

Detailed description

The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion 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]
• Anti-drug Antibody (ADA) [Time frame: Up to approximately 24 months]
• Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]

Eligibility criteria

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.

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

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing

Identifiers

NCT: NCT07753226 · SI-B036-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗