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)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 95
- 试验地点
- 2
- 主要终点
- Phase Ib/II: Objective response rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Study treatment
Participants will receive treatment during the first cycle. Participants with clinical benefits received more cycles of additional therapy. Administration will be discontinued due to disease progression or occurrence of intolerable toxicity or other reasons.
干预措施: SI-B001 (Drug)
Study treatment
Participants will receive treatment during the first cycle. Participants with clinical benefits received more cycles of additional therapy. Administration will be discontinued due to disease progression or occurrence of intolerable toxicity or other reasons.
干预措施: SI-B003 (Drug)
结局指标
主要结局
Phase Ib/II: Objective response rate (ORR)
时间窗: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Phase Ib: Dose Limited Toxicity (DLT)
时间窗: Up to approximately 24 months
The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).
Phase Ib: Maximum Tolerated dose (MTD) or maximum administered dose (MAD)
时间窗: Up to approximately 24 months
In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.
Phase Ib/II: Recommended Phase II Dose (RP2D)
时间窗: 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-B001+SI-B003.
次要结局
- Phase Ib/II: Disease control rate (DCR)(Up to approximately 24 months)
- Phase Ib/II: Progression-free survival (PFS)(Up to approximately 24 months)
- Phase Ib/II: Tmax(Up to approximately 24 months)
- Phase Ib/II: Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Phase Ib/II: Ctrough(Up to approximately 24 months)
- Phase Ib/II: Duration of response (DOR)(Up to approximately 24 months)
- Phase Ib/II: Cmax(Up to approximately 24 months)
- Phase Ib: AUC0-t(Up to approximately 24 months)
- Phase Ib/II: Anti-drug antibody (ADA)(Up to approximately 24 months)
- Phase Ib: T1/2(Up to approximately 24 months)
- Phase Ib: CL(Up to approximately 24 months)
- Phase Ib/II: Neutralizing antibody (Nab)(Up to approximately 24 months)