SCLC
Conditions
Interventions
Group 1:Ivonescimab combined with Cadonilimab plus EC
Group 2:Ivonescimab combined with Cadonilimab plus paclitaxel
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign a written informed consent form; 2. At the time of signing the informed consent form, age > = 18 years and 6 months; For Part 2: For ES-SCLC subjects who previously received only one PD-1/PD-L1 combination chemotherapy and progressed with effective prior treatment (PFS>=3 months), no more than two systemic chemotherapy regimens were used; 5. At least one measurable lesion (according to RECISTv1.1), and the lesion is suitable for repeated and accurate measurement. Note: Lesions that have previously received radiotherapy cannot be used as target lesions; Brain metastases should not be used as target lesions; 6. ECOG fitness status score of 0 or 1; 7. Expected survival > = 3 months; 8. Good organ function must be determined by the following requirements (test results from within 14 days prior to starting study treatment must be provided): (1) Hematology (no use of any blood components or cell growth factor supportive therapy within 7 days prior to study treatment): 1) Absolute value of neutrophils ANC > = 1.5 ×10^9/L (1,500/mm3) 2) Platelet count > = 100 ×10^9/L (100,000/mm3) 3) Hemoglobin > = 90 g/L (2) Kidneys: 1) Serum creatinine =28 g/L (4) Coagulation function: International Normalized Ratio (INR) and Activated Partial Coagulation Plastin Time (APTT) =50%; 9. Subjects must provide tumor tissue samples, either archived or newly acquired within 3 months prior to the first administration, with more than 10 unstained FFPE pathological slides (recently obtained tumor tissue samples preferred). Tumor lesions used for fresh tissue biopsy should not be treated as RECIST v1.1 target lesions unless the lesion is the only measurable lesion. If there is no tumor tissue sample archived within 3 months, and the investigator determines that biopsy may increase the subject's risk, and with the consent of the medical monitor, samples from archived tumor tissue beyond the 3 months may be collected. If more than 10 pathological slides cannot be provided, partial or full pathological slides may be waived upon investigator approval; 10. To explore efficacy-related biomarkers, subjects need to provide approximately 10 additional unstained pathological sections of FFPE tumor tissue samples. If unable to provide the study, exemption may be granted upon approval with the investigator, and participation in this study will not be affected; 11. Female subjects of childbearing potential must undergo a urine or serum pregnancy test within 3 days before the first administration (if the urine pregnancy test cannot confirm a negative result, a serum pregnancy test must be performed, based on the serum pregnancy result), and the result must be negative. If a female subject of reproductive potential has sex
Exclusion criteria
Exclusion criteria: 1. Simultaneous enrollment in another clinical study, unless it is a non-interventional study; 2. For subjects who have previously received immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibody, anti-CTLA-4 antibody, anti-TIGIT antibody, anti-LAG-3 antibody, etc.), immune checkpoint acrobatics (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, or any other treatment targeting the mechanism of tumor immune action; b) Previous systemic anti-angiogenic therapy, including but not limited to bevacizumab and its biosimilars, Endu, small molecule TKIs, ramulumab, etc. For PART 2: a) Cross-line PD-1/L1 inhibitor therapy: After failing to receive PD-1/L1 inhibitors combined with chemotherapy, the chemotherapy regimen is changed and the original PD-1/L1 inhibitor continues treatment. b) Subjects who have previously received immunotherapy other than PD-1/L1 inhibitors, including immune checkpoint inhibitors (e.g., anti-TIGIT antibodies, anti-LAG-3 antibodies, anti-CTLA-4 monoclonal antibodies), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies), immune cell therapy, or any other therapies targeting the mechanism of tumor immunity. c) Previous use of paclitaxel chemotherapy drugs. d) Previous systemic anti-angiogenic therapy, including but not limited to bevacizumab and its biosimilars, Endu, small molecule TKIs, ramulumab, etc. 3. During the screening period, imaging shows the tumor encircling important blood vessels or showing obvious necrosis or cavities, and the investigator determines that entry into the study will cause bleeding risk. 4. Having active autoimmune diseases requiring systemic treatment within the past two years (such as using disease-modifying drugs, corticosteroids, immunosuppressants). Replacement therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered systemic treatments. 5. History of non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy, or current presence of non-infectious pneumonia. 6. Presence of brainstem, meningeal metastases, spinal cord metastases, or compression. 7. Presence of active central nervous system (CNS) metastatic lesions; Subjects who have previously been treated with brain metastases (such as surgery or radiotherapy) are eligible if clinical stability for at least two weeks after treatment (counted from the first dose of the study drug) and discontinuation of corticosteroids 7 days before administration of the study drug; Untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no corticosteroid required, no metastatic lesion length >1.5 cm, no obvious perimetastases) can be enrolled. 8. Current uncontrolled comorbidities, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease, or gastritis, which may limit subjects from complying with study requirements or affect their ability to provide written informed consent due to mental illness/social conditions. 9. History of myocarditis, cardiomyopathy, or malignant arrhythmia. Unstable angina, myocardial infarction, congestive heart failure (grade 2 or higher as defined by the New York Heart Association functional classification) or vascular disease (such as aortic aneurysm at risk of rupture) or other cardiac damage that may affect the safety eval
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 6 month Progression Free Survival rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactChunxia Su
Shanghai Pulmonary Hospital
Outcome results
None listed