SCLC, Recurrent
Conditions
Keywords
SCLC, Ivonescimab, Paclitaxel Polymeric Micelles, Recurrent, Refractory, Recurrent small cell lung cancer, Refractory small cell lung cancer
Brief summary
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.
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.
Interventions
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.
DRUGIvonescimab
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.
Sponsors
Shaodong Hong
Akesobio
Shanghai Yizhong Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Ivonescimab 20 mg/kg intravenously every 3 weeks combined with paclitaxel polymeric micelles 230 mg/m2 intravenously every 3 weeks. Paclitaxel polymeric micelles will be administered for up to 4 cycles; ivonescimab may continue until disease progression, unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal, or up to approximately 2 years.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
CONTACTShaodong Hong Hong, M.D., Ph.D.
Outcome results
None listed