Paclitaxel Polymeric Micelles Plus Ivonescimab in Recurrent or Refractory SCLC

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: SCLC, Recurrent
• Intervention / Treatment: Drug: Paclitaxel Polymeric Micelles; Drug: Ivonescimab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shaodong Hong Hong, M.D., Ph.D.; Phone Number: +8615920527656; Email: hongshd@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Paclitaxel Polymeric Micelles; 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.; Drug: Ivonescimab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outcome Objective Response Rate (ORR) assessed by RECIST v1.1	The percentage of participants with a confirmed complete response or partial response, assessed by investigators according to RECIST version 1.1.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	The percentage of participants with complete response, partial response, or stable disease, assessed by investigators according to RECIST version 1.1.	Up to 36 months
Clinical Benefit Rate (CBR)	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.	Up to 36 months
Duration of Response (DOR)	The time from the first documented complete or partial response to the first documented disease progression, recurrence, or death from any cause.	Up to 36 months
Progression-Free Survival (PFS)	The time from first study treatment to documented disease progression or death from any cause, whichever occurs first.	Up to 36 months
Overall Survival (OS)	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.	Up to 36 months
Number of participants with Adverse Events	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.	From first dose through 30 days after the last study treatment, up to approximately 25 months

Collaborators and Investigators

• Sponsor: Shaodong Hong
• Collaborators: Shanghai Yizhong Pharmaceutical Co., Ltd.; Akesobio

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 24, 2026
• First Submitted That Met QC Criteria: September 14, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Refractory; Recurrent; SCLC; Ivonescimab; Paclitaxel Polymeric Micelles; Recurrent small cell lung cancer; Refractory small cell lung cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Recurrence; Small Cell Lung Carcinoma
• Other Study ID Numbers: 2026-FXY-020-NEIKE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data and data dictionaries from this investigator-initiated Phase II oncology study will not be shared at this time due to current sponsor/institutional policy, data governance requirements, and pending legal/ethics arrangements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No