Multicenter, Phase II Randomized Controlled Study of Adebrelimab Combined With Chemotherapy and Concurrent Low-Dose Radiotherapy (LDRT) for the Treatment of Extensive-Stage Small Cell Lung Cancer (SCLC)

Time from randomization to death from any cause. Unit of measure: median overall survival (months); hazard ratio (HR) and 95% confidence interval (CI); 12- and 24-month survival rates (%).

Assessment schedule: survival status assessed every 3 months after the end of treatment until death or study cut-off (up to 36 months).

Time from randomization to the earliest of radiologically documented progressive disease (per RECIST 1.1 assessed by the investigator) or death from any cause.

Unit of measure: median progression-free survival (months); hazard ratio (HR) and 95% confidence interval (CI); 6- and 12-month PFS rate (%).

Measurement tool: contrast-enhanced CT or MRI scanned every 6 weeks for the first 48 weeks, then every 12 weeks until disease progression, death, or study cut-off.

Defined as time from randomization to the earliest of radiologically documented second progression (per RECIST 1.1 assessed by the investigator ) or death from any cause.

Unit of measure: median PFS2 (months); hazard ratio (HR) and 95% CI; 6- and 12-month PFS2 rate (%).

Measurement tool: contrast-enhanced CT/MRI. Assessment schedule: imaging every 6 weeks during induction; every 4-6 weeks during maintenance; after first PD, every 6 weeks until second PD or death.

Proportion of randomized subjects with best overall response of complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 assessed by the investigator.

Unit of measure: percentage of patients (%); 95% confidence interval (Clopper-Pearson).

Assessment schedule: scans every 6 weeks for the first 48 weeks, then every 12 weeks until progression, death, or 36 months.

Proportion of randomized subjects achieving complete response (CR) or partial response (PR) per RECIST 1.1 assessed by the investigator.

Unit of measure: percentage of patients (%); 95% confidence interval (Clopper-Pearson).

Assessment schedule: scans every 6 weeks (±7 days) for the first 48 weeks, then every 12 weeks (±7 days) until progression, death, or 36 months; response determined by site investigator.

Time from first documented complete response (CR) or partial response (PR) per RECIST 1.1 (investigator assessment) until the date of documented progressive disease or death from any cause, whichever occurs first.

Unit of measure: median duration of response (months); 95% confidence interval of the median; 6- and 12-month response duration rate (%) Assessment schedule: imaging every 6 weeks for the first 48 weeks, then every 12 weeks until progression, death, or 36 months.

Maximum percentage reduction in the sum of longest diameters of target lesions relative to baseline per RECIST 1.1 assessed by the investigator.

Unit of measure: median percentage change (%); inter-quartile range (IQR); Assessment schedule: scans every 6 weeks for the first 48 weeks, then every 12 weeks until progression, death, or 36 months; tumor diameters measured by the site investigator.

Time from the date of first documented progressive disease (per RECIST 1.1, investigator assessment) to the date of death from any cause.

Unit of measure: median post-progression survival (months); hazard ratio (HR) and 95% confidence interval; 6- and 12-month survival rate (%).

Assessment schedule: survival status contacted every 3 months after progression until death, lost to follow-up, or study cut-off.

Number and percentage of participants experiencing AEs graded per CTCAE v5.0 by the treating investigator.

Unit of measure: incidence rate (%); number of events; severity distribution (Grade 1-5).

Measurement tool: investigator assessment using CTCAE v5.0. Assessment schedule: continuous monitoring from informed consent through 90 days after last dose of study drug; assessed at every study visit (baseline, weekly during cycle 1, then day 1 of each subsequent cycle, and at follow-up).

Number and percentage of participants experiencing serious adverse events (SAE) graded per CTCAE v5.0 by the treating investigator.

Unit of measure: incidence rate (%) of subjects with ≥1 SAE; number of events; severity distribution (Grade 1-5).

Measurement tool: investigator assessment using CTCAE v5.0. Assessment schedule: continuous monitoring from informed consent through 90 days after last dose of study drug. All SAEs reported within 24h of awareness.

Pearson correlation coefficient between baseline PD-L1 expression and overall survival (months).

Unit of measure: r (dimensionless) with 95% confidence interval. Measurement tool: PD-L1 IHC 22C3 pharmDx assay; PD-L1 tumor proportion score (TPS, %).

Assessment schedule: baseline diagnostic biopsy and, if clinically feasible, at the time of first and second tumor progression.

Pearson correlation coefficient between baseline PD-L1 TPS and PFS (months). Unit of measure: r (dimensionless) with 95% CI. Measurement tool: PD-L1 IHC 22C3 pharmDx assay; TPS (%). Assessment schedule: baseline tumor biopsy.

Pearson correlation coefficient between baseline peripheral blood neutrophil count and overall survival (months).

Unit of measure: r (dimensionless) with 95% CI. Measurement tool: automated hematology analyzer; absolute neutrophil count (10⁹/L).

Change in patient-reported global health status/quality of life score, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life scale (items 29 and 30).

Unit of measure: Mean change from baseline in score. Scale Details: The EORTC QLQ-C30 global health status/QoL scale is a 7-point Likert scale ranging from 1 ("Very poor") to 7 ("Excellent"). The raw score is linearly transformed to a 0-100 scale. Higher scores indicate a better quality of life.

Change in patient-reported functioning, as measured by the five functioning scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning.

Unit of Measure: Mean change from baseline in score for each scale. Scale Details: Each EORTC QLQ-C30 functioning scale consists of multiple items using a 4-point Likert scale (1="Not at all", 4="Very much"). Raw scores are linearly transformed to a 0-100 scale. For functioning scales, higher scores indicate a better level of functioning.

Change in patient-reported lung cancer symptoms, as measured by the symptom scales and items of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): dyspnoea, cough, haemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, and pain.

Unit of Measure: Mean change from baseline in score for each symptom scale/item.

Scale Details: EORTC QLQ-LC13 scales use a 4-point Likert scale (1="Not at all", 4="Very much"), transformed to a 0-100 scale. For symptom scales, higher scores indicate a greater severity of symptoms/worse outcome.

Treatment effect (adebrelimab + chemotherapy ± LDRT vs control) on overall survival in the pre-specified subgroup defined by baseline liver metastasis (yes vs no).

Unit of measure: hazard ratio (HR) with 95% confidence interval; median overall survival (months); 12-month survival rate (%).

Measurement tool: death from any cause determined by medical records or death registry.

Treatment effect on overall survival in the subgroup defined by baseline brain metastasis (yes vs no).

Unit of measure: HR with 95% CI; median OS (months); 12-month survival rate (%).

Measurement tool: death from any cause determined by medical records or death registry.

Treatment effect on PFS (RECIST 1.1, investigator) in the liver-metastasis subgroup (yes vs no).

Unit of measure: HR with 95% CI; median PFS (months); 6-month PFS rate (%). Measurement tool: CT/MRI.

Treatment effect on PFS in the brain-metastasis subgroup (yes vs no). Unit of measure: HR with 95% CI; median PFS (months); 6-month PFS rate (%). Measurement tool: CT/MRI.