Trial Title:
A Phase II Study of Ivonescimab Combined with Cadonilimab and Chemotherapy in Extensive-stage Small Cell Lung Cancer
NCT ID:
NCT06620796
Condition:
SCLC, Extensive Stage
Conditions: Official terms:
Small Cell Lung Carcinoma
Paclitaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Arm 1
Description:
Ivonescimab combined with Cadonilimab plus EC
Arm group label:
Arm1
Other name:
AK112+AK104 group
Intervention type:
Drug
Intervention name:
second-line group
Description:
AK112+AK104+paclitaxel
Arm group label:
Arm2
Other name:
AK112+AK104+paclitaxel
Summary:
The goal of this clinical trial is to investigate the efficacy, safety and tolerability
of Ivonescimab combined with Cadonilimab and chemotherapy in extensive-stage small cell
lung cancer patients. And also explore the potential biomarkers for predicting the
efficacy of Ivonescimab combined with Cadonilimab for extensive-stage small cell lung
cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent must be obtained before implementing any trial-related
procedures;
- Aged 18-80 years;
- Expected survival of more than 3 months;
- histologically or cytologically confirmed ES-SCLC according to the American Veterans
Cancer Association VALG staging system；
- Arm 1: subjects who have not received previous systemic therapy for extensive-stage
SCLC; Or patients who had received definitive chemoradiotherapy for limited-stage
small cell lung cancer but had disease progression > 6 months later;Arm 2：ES-SCLC
patients who progressed after only one PD-1/PD-L1 combination chemotherapy and had
response to previous treatment (PFS ≥ 3 months), no more than two systemic
chemotherapy regimens were used；
- The investigator confirms the presence of at least one measurable lesion according
to RECIST 1.1 criteria;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- Adequate hematologic function, defined as absolute neutrophil count (ANC) >= 1.5
x 10^9/L, platelet count >= 100 x 10^9/L, hemoglobin >= 90 g/L (without
transfusion history within 7 days);
- Adequate liver function, defined as total bilirubin level <= 1.5 times the upper
limit of normal (ULN) and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels <= 2.5 times ULN in all patients, or <= 5 times
ULN in patients with liver metastases;
- Adequate renal function, defined as serum creatinine <= 1.5 times ULN;
- Adequate coagulation function, defined as international normalized ratio (INR) or
prothrombin time (PT) <= 1.5 times ULN; for subjects receiving anticoagulant
therapy, INR/PT should be within the range planned by the anticoagulant;
- Women of childbearing potential must have a negative pregnancy test within 7 days
before starting treatment, and must use reliable contraceptive measures (such as
intrauterine device, contraceptive pills, and condoms) during the trial and for 30
days after the end of the trial; male subjects of reproductive potential must use
condoms for contraception during the trial and for 30 days after the end of the
trial;
- Willingness to comply with regular follow-up visits and trial requirements.
- Participants were required to provide 10 or more unstained FFPE pathological slides
(preferably newly obtained tumor tissue) archived or freshly obtained within 3
months prior to the first dose of medication. Tumor lesions used for fresh-tissue
biopsy should not be used as RECIST v1.1 target lesions unless they are the only
measurable lesion. The collection of archived tumor-tissue samples beyond 3 months
of age was permitted, with the consent of the medical monitor, if no samples were
available within 3 months of age and biopsy, as judged by the investigator, might
increase the risk to the subject. If more than 10 slides were not available, some or
all of the slides could be waived with investigator approval；
- Participants were required to provide approximately 10 unstained FFPE tumor tissue
slides for efficacy biomarker exploration. If it cannot be provided, it can be
exempted after approval from the investigator and will not affect the Participants
participation in this study；
Exclusion Criteria:
- Currently participating in interventional clinical research treatment;
- For Arm 1: a) Prior 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 agonists (e.g. ICOS, CD40, CD137, GITR, OX40
antibody, etc.), immune cell therapy, and any treatment targeting the tumor immune
mechanism; b) previous systemic anti-angiogenic therapy, including but not limited
to bevacizumab small molecule TKI, etc. For Arm 2:
a) PD-1/L1 inhibitor crossover therapy: after the failure of PD-1/L1 inhibitor
combined with chemotherapy, the chemotherapy regimen was changed and the original
PD-1/L1 inhibitor was given again. b) Prior immunotherapy other than PD-1/L1
inhibitors, including immune checkpoint inhibitors (e.g., anti-TIGIT antibody,
anti-LAG-3 antibody, etc., anti-CTLA-4 monoclonal antibody), immune checkpoint
agonists (e.g. ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy,
and any treatment targeting the mechanism of tumor immune action. c) previous
treatment with a taxol chemotherapeutic agent. d) previous systemic anti-angiogenic
therapy, including but not limited to bevacizumab, small molecule TKI, etc.
- Imaging during the screening period showed that the tumor was surrounded by
important blood vessels or had obvious necrosis or cavities, and the investigator
judged that the entry of the study would cause bleeding risk.
- active autoimmune disease requiring systemic treatment within the past 2 years
(e.g., with disease-modifying medications, corticosteroids, immunosuppressants).
Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid
replacement for adrenal or pituitary insufficiency) is not considered a systemic
treatment.
- history of noninfectious pneumonia/interstitial lung disease requiring systemic
glucocorticoid treatment or current noninfectious pneumonia.
- History of brain stem, meningeal metastasis, spinal cord metastasis or
compression.presence of active central nervous system (CNS) metastases; Participants
who had previously been treated for brain metastases (e.g., surgery, radiotherapy)
were allowed if they were clinically stable for at least two weeks after treatment
(calculated from the time of the first administration of the study drug) and if
corticosteroids were discontinued 7 days before the administration of the study
drug. Participants with untreated, asymptomatic brain metastases (i.e., no
neurologic symptoms, no need for corticosteroids, no brain metastases measuring
>1.5 cm in the greatest dimension, and no substantial premetastatic edema) were
eligible for enrollment
- presence of current uncontrolled coexisting medical conditions, including but not
limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic
disorder, severe active peptic ulcer disease, or gastritis, or mental illness/social
condition that would limit compliance with study requirements or affect the
participant's ability to provide written informed consent;
- previous history of myocarditis, cardiomyopathy, and malignant arrhythmia. The
presence of unstable angina, myocardial infarction, congestive heart failure (New
York Heart Association functional class 2 or higher), or vascular disease (e.g.,
aortic aneurysm at risk for rupture) that required hospitalization within 12 months
before the first dose of the study drug or other cardiac impairment (e.g.,
uncontrolled arrhythmias, myocardial ischemia) that could affect the safety
evaluation of the study drug; The patient had a history of esophagogastric varices,
severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula,
gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal
bleeding within 6 months before the first dose of medication. Any arterial
thromboembolic event, venous thromboembolic event of NCI CTCAE version 5.0 or
higher, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or
hypertensive encephalopathy occurred 6 months before the first dose. An acute
exacerbation of chronic obstructive pulmonary disease occurred within 1 month before
the first dose, except for infusion-related thrombosis that had occurred for more
than 4 weeks.
- history of severe bleeding tendency or coagulopathy; Clinically significant bleeding
symptoms within 1 month before the first dose of medication, including but not
limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or coughing
up ≥1 teaspoon of blood or small blood clot or only coughing up blood without
sputum, and those with blood in sputum were allowed), nasal bleeding (excluding
epistaxis and retraction of nasal bleeding); Continuous antiplatelet or
anticoagulant therapy had been administered within 10 days before the first dose.
- lack of resolution of toxicity from prior antineoplastic therapy, defined as failure
to return to NCI CTCAE version 5.0 grade 0 or 1 or levels specified in the
inclusion/exclusion criteria, with the exception of alopecia. Subjects with
irreversible toxicity that was not expected to worsen with study drug administration
(e.g., hearing loss) may be enrolled after consultation with the medical monitor.
Subjects with long-term radiation-induced toxicity that, in the judgment of the
investigator, did not recover from, may be included in the study.
- serious infection within 4 weeks before the first dose, including but not limited to
coexisting conditions requiring hospitalization, sepsis, or severe pneumonia; Active
infection (excluding antiviral therapy for hepatitis B or hepatitis C) that had
received systemic anti-infective therapy within 2 weeks before the first dose.
- history of immunodeficiency; HIV antibody positive; Long-term use of systemic
corticosteroids or other immunosuppressive agents is ongoing.
- Subjects with known active pulmonary tuberculosis should be excluded by clinical
examination (e.g., sputum test, chest X-ray, etc.); Known active syphilis infection.
- history of allogeneic organ transplantation and allogeneic hematopoietic stem cell
transplantation.
- presence of pleural effusion, pericardial effusion, or ascites with clinical
symptoms or requiring repeated drainage.
- subjects with active hepatitis B (HBsag-positive and HBV-DNA > 500 copies /ml or
higher than the lower limit of detection); Subjects with active hepatitis C (HCV
antibody-positive).
- had a major surgical procedure or major trauma within 30 days before or within 30
days after the first dose (at the discretion of the investigator); Minor local
procedures (excluding peripherally inserted central catheters and intravenous-access
ports) had been performed within 3 days before the first dose.
- received live attenuated influenza vaccine within 30 days before the first dose or
plan to receive live attenuated influenza vaccine during the study and cannot
receive live attenuated influenza vaccine within 90 days after treatment after the
last dose of the study drug.
- known allergy to any component of any study drug; A history of severe
hypersensitivity reactions to other monoclonal antibodies was known.
- known history of mental illness, substance abuse, alcohol or drug abuse.
- pregnant or lactating women.
- The presence of any past or current medical conditions, treatments, or laboratory
abnormalities that may confound the results of the study, preclude full
participation in the study, or participation in the study may not be in the best
interest of the subject
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Start date:
September 30, 2024
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Shanghai Pulmonary Hospital, Shanghai, China
Agency class:
Other
Source:
Shanghai Pulmonary Hospital, Shanghai, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06620796
