A Phase II Study of Paclitaxel Polymeric Micelles Combined With Ivonescimab in Patients With Recurrent or Refractory Small Cell Lung Cancer After Failure of Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Outcome Objective Response Rate (ORR) assessed by RECIST v1.1
研究概览
简要总结
This is a multicenter, open-label, single-arm phase 2 study evaluating the efficacy and safety of ivonescimab combined with paclitaxel polymeric micelles in adults with recurrent or refractory small cell lung cancer after failure of platinum-based chemotherapy and anti-PD-1/PD-L1 therapy.
详细描述
This multicenter, open-label, single-arm phase II investigator-initiated study evaluates the efficacy and safety of ivonescimab combined with paclitaxel polymeric micelles in adults with recurrent or refractory small cell lung cancer after failure of platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. Participants will receive ivonescimab 20 mg/kg intravenously on Day 1 every 3 weeks, followed at least 30 minutes later by paclitaxel polymeric micelles 230 mg/m² intravenously over at least 3 hours on Day 1 every 3 weeks. Paclitaxel polymeric micelles will be administered for up to 4 cycles. Ivonescimab may continue for up to 2 years or until disease progression, initiation of new antitumor therapy, unacceptable toxicity, withdrawal of consent, death, or another protocol-defined reason for discontinuation. Tumor response will be assessed by investigators using RECIST v1.1 every 6 weeks during the first 12 months and every 9 weeks thereafter. The primary endpoint is objective response rate. Secondary endpoints include disease control rate, clinical benefit rate, duration of response, progression-free survival, overall survival, and safety assessed using NCI CTCAE version 5.0.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who have signed informed consent and agree to comply with the protocol.
- •Age ≥ 18 years.
- •Histologically or cytologically confirmed relapsed small-cell lung cancer after failure of platinum-based chemotherapy and PD-1/PD-L1 monoclonal antibody treatment.
- •At least one measurable lesion according to RECIST v1.
- •ECOG performance status 0 or
- •Expected survival time ≥ 3 months.
- •Recovery of prior anti-tumor therapy toxicities to ≤ Grade 1 (NCI-CTCAE v5.0), except alopecia, fatigue, hyperpigmentation, and stabilized thyroid dysfunction (on hormone replacement) as specified in protocol.
- •Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%.
- •Adequate organ function: ANC ≥ 1.5×10^9/L, platelets ≥ 100×10^9/L, hemoglobin ≥ 90 g/L.
- •Total bilirubin ≤ 1.5×ULN (≤ 3×ULN if liver metastases); AST and ALT ≤ 2.5×ULN (≤ 5.0×ULN if liver metastases).
- •Creatinine ≤ 1.5×ULN or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault).
- •INR ≤ 1.5; APTT ≤ 1.5×ULN.
- •Women of childbearing potential: negative pregnancy test within 7 days before first dosing and non-lactating.
- •Effective contraception from screening through 6 months after end of treatment for all patients with reproductive potential.
排除标准
- •History of hypersensitivity to paclitaxel micelles, ivonescimab (YS11/YS), or components of these investigational products, or structurally related agents.
- •Prior systemic therapy with taxanes and/or anti-VEGF monoclonal antibodies.
- •Major surgery within 28 days before first investigational treatment.
- •Antitumor treatment within 4 weeks (or 5 half-lives for biologics, whichever is shorter), including chemotherapy, targeted therapy, biologics, immunotherapy, curative radiotherapy, major surgery, or large-field radiotherapy; small-molecule targeted therapy within 5 days before first dose (as protocol details).
- •Use of CYP3A/CYP2C inhibitors or inducers within 7 days before first dose, or need to continue during study.
- •Use of traditional Chinese anti-tumor herbal medicines within 7 days before first dose, or need to continue during study.
- •Ongoing use of drugs known to prolong QT interval or induce torsades during study.
- •Symptomatic CNS involvement (including symptomatic brain metastases); brain-metastasis patients previously on steroids must be tapered and off steroids for ≥14 days unless protocol allows exceptions.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Tumor encasement/invasion of major thoracoabdominal/other vital vessels judged unsafe for protocol treatment.
- •Clinically significant bleeding within 3 weeks before informed consent (e.g., hemoptysis, GI bleeding, bleeding ulcer).
- •Inflammatory bowel disease, major bowel resection history, immune-related colitis, bowel obstruction, chronic diarrhea, or Gilbert syndrome.
- •Other malignancy within 5 years, except adequately controlled basal cell carcinoma, cervical CIS, or DCIS >3 years.
- •Serious cardiac/cerebrovascular disease: NYHA class ≥2 heart failure, acute coronary syndrome within 6 months, or stroke/TIA/hemorrhagic stroke within 6 months.
- •Significant arrhythmia (complete LBBB, third-degree AV block, uncontrolled ventricular/atrial arrhythmia; stable controlled arrhythmia exceptions may apply).
- •Active unstable thromboembolic disease requiring treatment within 6 months (except >4-week old peripheral line thrombosis).
- •Uncontrolled systemic diseases likely to interfere with protocol conduct, including uncontrolled hypertension, diabetes, active bleeding, active hepatitis B/C/HIV (including HBV DNA >10000 copies/mL when HBsAg positive), or other active infection.
- •Autoimmune disease requiring systemic treatment in prior 2 years (excluding replacement hormones).
- •Current or clinically significant history of ILD, or ILD/grade ≥2 radiation pneumonitis.
- •Severe neurologic or psychiatric disease.
- •Unhealed wound, ulcer, or fracture within 4 weeks before informed consent.
- •Planned or received live vaccine within 28 days before randomization/first dose.
- •Pregnancy or breastfeeding.
- •Any other condition the investigator judges to make trial participation inappropriate.
研究组 & 干预措施
Experimental: Paclitaxel Polymeric Micelles plus Ivonescimab
Ivonescimab 20 mg/kg is administered intravenously on Day 1 every 3 weeks. At least 30 minutes later, paclitaxel polymeric micelles 230 mg/m² are administered intravenously over at least 3 hours on Day 1 every 3 weeks. Paclitaxel polymeric micelles are given for up to 4 cycles. Ivonescimab continues for up to 2 years or until disease progression, initiation of new antitumor therapy, unacceptable toxicity, withdrawal of consent, death, or another protocol-defined reason for discontinuation.
干预措施: Paclitaxel Polymeric Micelles (Drug)
Experimental: Paclitaxel Polymeric Micelles plus Ivonescimab
Ivonescimab 20 mg/kg is administered intravenously on Day 1 every 3 weeks. At least 30 minutes later, paclitaxel polymeric micelles 230 mg/m² are administered intravenously over at least 3 hours on Day 1 every 3 weeks. Paclitaxel polymeric micelles are given for up to 4 cycles. Ivonescimab continues for up to 2 years or until disease progression, initiation of new antitumor therapy, unacceptable toxicity, withdrawal of consent, death, or another protocol-defined reason for discontinuation.
干预措施: Ivonescimab (Drug)
结局指标
主要结局
Outcome Objective Response Rate (ORR) assessed by RECIST v1.1
时间窗: Up to 36 months
The percentage of participants with a confirmed complete response or partial response, assessed by investigators according to RECIST version 1.1.
次要结局
- Disease Control Rate (DCR)(Up to 36 months)
- Clinical Benefit Rate (CBR)(Up to 36 months)
- Duration of Response (DOR)(Up to 36 months)
- Progression-Free Survival (PFS)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)
- Number of participants with Adverse Events(From first dose through 30 days after the last study treatment, up to approximately 25 months)
研究者
Shaodong Hong
Principle Inverstigator
Sun Yat-sen University