Paclitaxel Polymeric Micelles Plus Ivonescimab in Recurrent or Refractory SCLC

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.

Inclusion criteria

• 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 v1.1.
• ECOG performance status 0 or 1.
• 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.

Exclusion criteria

• 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.