A Study of SI-B036 in Patients With Locally Advanced or Metastatic 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 Solid Tumors

Overview

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

• 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]
• 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]
• 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]
• ADA (anti-drug antibody) [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 solid tumors;
• Agree to provide archived tumor tissue specimens from primary or metastatic lesions within 2 years or fresh tissue samples;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• ECOG performance status score of 0 or 1;
• Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• Organ function levels must meet the requirements;
• Coagulation function: International Normalized Ratio ≤1.5, and Activated Partial Thromboplastin Time ≤1.5 × ULN;
• Urine protein ≤2+ or ≤1000 mg/24h;
• 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;
• 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

• Use of chemotherapy, biological therapy, immunotherapy, etc. within 4 weeks or 5 half-lives prior to the first dose;
• Receipt of immunosuppressive therapy within 2 weeks prior to the first dose;
• History of severe cardiac or cerebrovascular disease;
• QT interval prolongation, complete left bundle branch block, etc.;
• 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 event requiring therapeutic intervention within 6 months prior to the first dose;
• Poorly controlled hypertension;
• Diabetic patients with poorly controlled blood glucose;
• History of ILD requiring steroid therapy, or current ILD, or ≥ grade 2 radiation pneumonitis;
• Concomitant pulmonary disease causing severe respiratory impairment;
• Active central nervous system metastases;
• History of allergy to recombinant humanized or human-mouse chimeric antibodies, or hypersensitivity to any excipient component of SI-B036;
• Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Positive for human immunodeficiency virus antibody, 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 study drug;
• 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;
• Imaging findings indicating tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart;
• Study participants with clinically significant bleeding or a clear 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 enrollment 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

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07606612 · SI-B036-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗