Extensive-stage Small Cell Lung Cancer (ES-SCLC)
Conditions
Brief summary
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.
Interventions
DRUGIvonescimab
Administered intravenously at a specified dose and frequency.
DRUGCadonilimab
Administered intravenously at a specified dose and frequency.
DRUGAK117
Administered intravenously at a specified dose and frequency.
DRUGEtoposide
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.
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC). * No prior systemic therapy for ES-SCLC. * At least one measurable lesion as defined by RECIST v1.1. * Age 18 to 75 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function.
Exclusion criteria
* Active or untreated central nervous system (CNS) metastases (Treated, stable brain metastases are allowed). * History of severe hypersensitivity to monoclonal antibodies. * Active autoimmune disease requiring systemic treatment within the past 2 years. * Significant cardiovascular disease. * Active hepatitis B or C, or HIV infection. * Interstitial lung disease or non-infectious pneumonitis. * Significant bleeding tendency or risk, including tumor invasion of major blood vessels. * Pregnancy or lactation. * Other active malignancies within 5 years prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 2 years. | 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. |
| Incidence of Adverse Events (AEs) | From first dose up to 90 days after last dose. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | Up to approximately 2 years. | 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. |
| Progression-Free Survival (PFS) | Up to approximately 2 years. | 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. |
| Disease Control Rate (DCR) | Up to approximately 2 years. | The proportion of participants achieving a BOR of CR, PR, or Stable Disease (SD), as assessed by the investigator per RECIST v1.1. |
| Serum concentrations of Ivonescimab, Cadonilimab, and AK117 | Up to approximately 2 years. | Serum concentrations of Ivonescimab, Cadonilimab, and AK117 will be measured to characterize the pharmacokinetic (PK) profiles. |
| Incidence of Anti-drug Antibodies (ADA) | Up to approximately 2 years. | The immunogenicity will be assessed by the incidence of participants who develop detectable anti-drug antibodies (ADA) against Ivonescimab, Cadonilimab, and/or AK117. |
| Overall Survival (OS) | Up to approximately 5 years. | OS is defined as the time from the start of study treatment to death from any cause. |
| Duration of Response (DoR) | Up to approximately 2 years. | 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. |
Countries
China
Contacts
Primary ContactWenting Li
Outcome results
None listed