The goal of this clinical trial is to learn if different combinations of a drug called Ivonescimab, along with chemotherapy and other investigational drugs, are safe and effective for the initial treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). The main questions the study aims to answer are: * What side effects do participants experience from these combination treatments? * How well do the treatments work to shrink tumors? Researchers will compare three groups to see which combination works best. All participants will receive Ivonescimab and chemotherapy (etoposide and carboplatin). The differences are: * Group 1 will also receive an additional drug called AK117. * Group 2 will also receive a different additional drug called Cadonilimab. * Group 3 will receive Ivonescimab and chemotherapy only. Participants will: * Be assigned by chance to one of the three groups. * Undergo an initial treatment phase (about 3 months), receiving chemotherapy plus the specific study drugs for their group. * If the treatment is effective and side effects are manageable, continue with a maintenance phase using only the study drugs (without chemotherapy) for up to 2 years. * Attend regular clinic visits for check-ups, blood tests, and imaging scans (like CT scans) to see how they are responding to the treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
Administered intravenously at a specified dose and frequency.
Administered intravenously at a specified dose and frequency.
Administered intravenously at a specified dose and frequency.
Administered intravenously at 100 mg/m² on Days 1-3 of each 3-week cycle for 4 cycles.
Administered intravenously at AUC 5 on Day 1 of each 3-week cycle for 4 cycles.
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, China
RECRUITINGShanghai Pulmonary Hospital Affiliated to Tongji University
Shanghai, Shanghai Municipality, China
RECRUITINGObjective Response Rate (ORR)
The proportion of participants achieving a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Up to approximately 2 years.
Incidence of Adverse Events (AEs)
The number and percentage of participants experiencing any Adverse Event (AE). An AE is defined as any untoward medical occurrence in a participant administered a study drug, which may not have a causal relationship with the treatment. Severity will be graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Time frame: From first dose up to 90 days after last dose.
Disease Control Rate (DCR)
The proportion of participants achieving a BOR of CR, PR, or Stable Disease (SD), as assessed by the investigator per RECIST v1.1.
Time frame: Up to approximately 2 years.
Duration of Response (DoR)
For responders (participants achieving CR or PR), DoR is defined as the time from the first documented evidence of CR or PR until the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1.
Time frame: Up to approximately 2 years.
Time to Response (TTR)
For responders (participants achieving CR or PR), TTR is defined as the time from the start of study treatment to the first documented objective response (CR or PR), per RECIST v1.1.
Time frame: Up to approximately 2 years.
Progression-Free Survival (PFS)
PFS is defined as the time from the start of study treatment to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Time frame: Up to approximately 2 years.
Overall Survival (OS)
OS is defined as the time from the start of study treatment to death from any cause.
Time frame: Up to approximately 5 years.
Serum concentrations of Ivonescimab, Cadonilimab, and AK117
Serum concentrations of Ivonescimab, Cadonilimab, and AK117 will be measured to characterize the pharmacokinetic (PK) profiles.
Time frame: Up to approximately 2 years.
Incidence of Anti-drug Antibodies (ADA)
The immunogenicity will be assessed by the incidence of participants who develop detectable anti-drug antibodies (ADA) against Ivonescimab, Cadonilimab, and/or AK117.
Time frame: Up to approximately 2 years.
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