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

Официальное название

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)

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

• Phase Ib/II: Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Disease control rate (DCR) [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Duration of response (DOR) [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Progression-free survival (PFS) [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Cmax [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Tmax [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Ctrough [Срок оценки: Up to approximately 24 months]
• Phase Ib: T1/2 [Срок оценки: Up to approximately 24 months]
• Phase Ib: AUC0-t [Срок оценки: Up to approximately 24 months]
• Phase Ib: CL [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Anti-drug antibody (ADA) [Срок оценки: Up to approximately 24 months]
• Phase Ib/II: Neutralizing antibody (Nab) [Срок оценки: Up to approximately 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Pulmonary Hospital — Шанхай

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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