Paclitaxel Polymeric Micelles Plus Ivonescimab in Recurrent or Refractory SCLC

Prior treatment

• 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.
• 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.
• Clinically significant bleeding within 3 weeks before informed consent (e.g., hemoptysis, GI bleeding, bleeding ulcer).
• Autoimmune disease requiring systemic treatment in prior 2 years (excluding replacement hormones).
• Unhealed wound, ulcer, or fracture within 4 weeks before informed consent.
• Planned or received live vaccine within 28 days before randomization/first dose.

Other illness

• Inflammatory bowel disease, major bowel resection history, immune-related colitis, bowel obstruction, chronic diarrhea, or Gilbert syndrome.
• 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.
• Current or clinically significant history of ILD, or ILD/grade ≥2 radiation pneumonitis.
• Severe neurologic or psychiatric disease.
• Any other condition the investigator judges to make trial participation inappropriate.

Lab values

• Ongoing use of drugs known to prolong QT interval or induce torsades during study.

Age

• Other malignancy within 5 years, except adequately controlled basal cell carcinoma, cervical CIS, or DCIS \>3 years.

Other

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Tumor encasement/invasion of major thoracoabdominal/other vital vessels judged unsafe for protocol treatment.
• Pregnancy or breastfeeding.

• 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.