A Study of SI-B001+SI-B003± Chemotherapy in the Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer

Official title

A Phase Ib/II Clinical Trial to Evaluate the Safety and Efficacy of SI-B001+SI-B003 With or Without Chemotherapy (SI-B001+SI-B003± Chemotherapy) in the Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

Overview

Phase Ib: To observe the safety and tolerability of the combination of SI-B001 and SI-B003, and to determine the recommended dose of phase II clinical study (RP2D) in the indication of locally advanced or metastatic non-small cell lung cancer. Phase II: To evaluate the efficacy of SI-B001+SI-B003 combination with or without chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer.

Interventions

• Drug SI-B001
  Administration by intravenous infusion
• Drug SI-B003
  Administration by intravenous infusion

Primary outcome measures

• Phase Ib/II: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Objective response rate (ORR) [Time frame: Up to approximately 24 months]
• Phase Ib: Dose Limited Toxicity (DLT) [Time frame: Up to approximately 24 months]
• Phase Ib: Maximum Tolerated dose (MTD) or maximum administered dose (MAD) [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Phase Ib/II: Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Disease control rate (DCR) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Duration of response (DOR) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Progression-free survival (PFS) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Cmax [Time frame: Up to approximately 24 months]
• Phase Ib/II: Tmax [Time frame: Up to approximately 24 months]
• Phase Ib/II: Ctrough [Time frame: Up to approximately 24 months]
• Phase Ib: T1/2 [Time frame: Up to approximately 24 months]
• Phase Ib: AUC0-t [Time frame: Up to approximately 24 months]
• Phase Ib: CL [Time frame: Up to approximately 24 months]
• Phase Ib/II: Anti-drug antibody (ADA) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Neutralizing antibody (Nab) [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 restrictions;
• Age ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Subjects must agree to complete ctDNA testing during the screening period;
• Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) patients;
• Agree to provide archived or fresh tumor tissue samples from primary or metastatic lesions;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• Performance status score: ECOG ≤1;
• Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
• Organ function levels must meet the requirements without transfusion, albumin, colony-stimulating factors, any cell growth factors, and/or platelet-raising drugs within 14 days before the first dose of the study drug;
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
• Urine protein ≤1+ or ≤1000 mg/24h;
• Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 24 weeks after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.

Exclusion criteria

• Prior to signing the informed consent form, relevant genetic alterations were indicated;
• For patients enrolled in Phase II, any of the following conditions apply: a) Patients suitable for and willing to undergo local therapy; b) Patients who have received systemic chemotherapy;
• Symptomatic brain parenchymal or leptomeningeal metastases, deemed ineligible by the investigator;
• Participation in any other clinical trial within 4 weeks prior to the administration of this trial's investigational product (based on the last dose date);
• Use of chemotherapy, biologic therapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose, or palliative radiotherapy, small-molecule targeted therapy, or other antitumor treatments within 2 weeks before the first dose;
• Major surgery (as defined by the investigator) within 4 weeks prior to the first dose;
• Requirement for systemic corticosteroids or immunosuppressive therapy within 2 weeks before the study drug administration;
• Pulmonary diseases graded as ≥3 according to NCI-CTCAE v5.0; history of interstitial lung disease (ILD), current ILD, or suspected ILD during screening;
• Concurrent pulmonary disease resulting in clinically significant respiratory impairment;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before screening (excluding catheter-related thrombosis);
• Active infection requiring intravenous anti-infective therapy;
• Imaging findings indicating tumor invasion or encasement of major thoracic, cervical, or pharyngeal blood vessels, with a risk of bleeding post antitumor therapy;
• Prior immunotherapy leading to ≥Grade 3 immune-related adverse events (irAE) or ≥Grade 2 immune-related myocarditis;
• Use of live attenuated vaccines within 4 weeks before the first dose of the study drug;
• Use of immunomodulatory drugs within 14 days before the first dose of the study drug;
• Patients at risk of active autoimmune diseases or with a history of autoimmune diseases;
• History of other malignancies within 5 years before the first dose;
• Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
• Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg);
• History of severe cardiovascular or cerebrovascular diseases;
• Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
• History of allogeneic stem cell, bone marrow, or organ transplantation;
• History of hypersensitivity to recombinant humanized antibodies or any excipients of SI-B001 or SI-B003;
• History of autologous or allogeneic stem cell transplantation;
• Pregnant or lactating women;
• Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

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

• Shanghai Pulmonary Hospital — Shanghai

Identifiers

NCT: NCT05949606 · SI-B001-SI-B003-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗