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.

• Paclitaxel Polymeric Micelles (Drug): Paclitaxel polymeric micelles 230 mg/m² are administered intravenously over at least 3 hours on Day 1 of each 3-week cycle, at least 30 minutes after ivonescimab infusion. Treatment is given for a maximum of 4 cycles or until initiation of new antitumor therapy, unacceptable toxicity, withdrawal of consent, death, or another protocol-defined reason for discontinuation.
• Ivonescimab (Drug): Ivonescimab 20 mg/kg is administered intravenously on Day 1 of each 3-week cycle. It is administered before paclitaxel polymeric micelles. Treatment 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.

Primary outcomes

• Outcome Objective Response Rate (ORR) assessed by RECIST v1.1 [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.

Secondary outcomes

• Disease Control Rate (DCR) [Up to 36 months]: The percentage of participants with complete response, partial response, or stable disease, assessed by investigators according to RECIST version 1.1.
• Clinical Benefit Rate (CBR) [Up to 36 months]: The percentage of participants with an objective response or stable disease lasting at least 4 months, assessed by investigators according to RECIST version 1.1.
• Duration of Response (DOR) [Up to 36 months]: The time from the first documented complete or partial response to the first documented disease progression, recurrence, or death from any cause.
• Progression-Free Survival (PFS) [Up to 36 months]: The time from first study treatment to documented disease progression or death from any cause, whichever occurs first.
• Overall Survival (OS) [Up to 36 months]: The time from first study treatment to death from any cause; participants alive at analysis are censored at the last known alive date or clinical cutoff date.
• Number of participants with Adverse Events [From first dose through 30 days after the last study treatment, up to approximately 25 months]: Incidence and severity of adverse events, serious adverse events, laboratory abnormalities, vital-sign abnormalities, physical examination findings, and electrocardiogram abnormalities; severity is assessed using NCI CTCAE version 5.0.

Sex: All, ages: 18 Years to any

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.