CAPSTONE-1 Phase 3: Adebrelimab Combo in 1L ES-SCLC Treatment

Poor prognosis and few treatment choices characterize extensive-stage small-cell lung cancer (ES-SCLC). However, previous phase 3 trials using immunotherapy for ES-SCLC have demonstrated strong clinical activity. Researchers compared adebrelimab (SHR-1316), a new anti-PD-L1 antibody, to standard chemotherapy for the initial treatment of ES-SCLC, intending to gauge its efficacy and safety.

The CAPSTONE-1 study was a randomized, double-blind, placebo-controlled phase 3 trial among 47 tertiary hospitals in China. The criteria included patients between 18 and 75 with a histologically or cytologically confirmed ES-SCLC diagnosis and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients who met the inclusion criteria were given either adebrelimab (20 mg/kg, day 1 of each cycle) or a matching placebo, with four to six cycles of carboplatin (area under the curve 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m2 of body-surface area, on days 1-3 of each cycle), and then maintenance therapy with adebrelimab or placebo. All medicines were administered every 21 days. Patients were randomly put into one of four treatment groups based on their liver metastases, brain metastases, and lactate dehydrogenase concentration. This was done with the help of a centralized, interactive web-based response system. OS was the primary objective for patients who received any study drug. The as-treated population was analyzed for safety.

Patients were enrolled and randomly assigned between December 26, 2018, and September 4, 2020; 230 (50%) received adebrelimab with chemotherapy (adebrelimab group), and 232 (50%) received placebo plus chemotherapy (placebo group) (placebo group). The median follow-up time was 13.5 months (IQR 8.9-20.1) as of the data cutoff date of October 8, 2021. The adebrelimab group had a substantially longer median overall survival (median 15.3 months; 95% confidence interval [CI] 13.2-17.5 months; hazard ratio 0.72; 95% CI 0.58-0.90; one-sided p=0. 0017) than the placebo group (12. 8 months; 11. 3-13. 7 months). Neutrophil count decreased (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), white blood cell count decreased (106 [46%] and 88 [38%]), platelet count decreased (88 [38%] and 78 [34%]), and anemia (64 [28%] and 66 [28%]) were the most common treatment-related grade 3 or 4 adverse events. There were 89 patients in the adebrelimab group (39%) and 66 patients in the placebo group (28%) who experienced major side events due to their treatment. Four deaths were associated with the treatments: two in the adebrelimab group (from respiratory failure, interstitial lung disease, and pneumonia) and two in the placebo group (multiple organ dysfunction and unknown cause of death).

Overall survival was considerably enhanced in patients with ES-SCLC when adebrelimab was added to chemotherapy, and the combination had an acceptable safety profile.

Source: https://pubmed.ncbi.nlm.nih.gov/35576956/

Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03711305

Wang, J., Zhou, C., Yao, W., Wang, Q., Min, X., Chen, G., Xu, X., Li, X., Xu, F., Fang, Y., Yang, R., Yu, G., Gong, Y., Zhao, J., Fan, Y., Liu, Q., Cao, L., Yao, Y., Liu, Y., Li, X., … CAPSTONE-1 Study Group (2022). Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. Oncology, 23(6), 739–747. https://doi.org/10.1016/S1470-2045(22)00224-8