Prolgolimab with Chemotherapy as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer

• Published in: European journal of cancer (1990) 2025-01, Vol.217, p.115255, Article 115255
• Main Authors: Laktionov, K., Smolin, A., Stroyakovskiy, D., Moiseenko, V., Dvorkin, M., Andabekov, T., Cheng, Y., Liu, B., Kozlov, V., Odintsova, S., Dvoretsky, S., Mochalova, A., Urda, M., Yi, T., Li, X., László, U., Müller, V., Bogos, K., Fadeeva, N., Musaev, G., Liu, Q., Kirtbaya, D., Shi, J., Gladkov, O., Narimanov, M., Semiglazova, T., Khasanova, A., Chovanec, J., Andrašina, I., Szabová, A., Rosinská, O., Sudekova, D., Zsolt, P-S., Ran, F., Sun, M., Jiang, O., Chen, R., Zhao, E., Liu, C., Tan, W., Pirmagomedov, A., Poddubskaya, E., Kislov, N., Shumskaya, I., Sorokina, I., Zinkina-Orikhan, A., Linkova, Yu, Fogt, S., Liaptseva, D., Siliutina, A., Basova, O., Kryukov, F.
• Format: Article
• Language: English
• Subjects: Anti-PD-1; Non-small cell lung cancer; PD-L1 expression; Prolgolimab
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2025.115255

Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing ‘LALA’ mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC). 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months). The primary endpoint was overall survival (OS). After a median follow-up of 18 months, the median OS was not reached (95% CI, 22.28 – NA) in the prolgolimab-combination group vs 14.6 months (95% CI, 11.73 – 19.15) in the placebo-combination group (HR, 0.51; 95% CI, 0.35 – 0.73, p = 0.0001). The OS improvement was independent of PD-L1 status. Median progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was 7.7 months in the prolgolimab-combination group and 5.5 months in the placebo-combination group (HR, 0.65; 95% CI, 0.49 – 0.85, p = 0.0004). The only adverse events that were reported in at least 10% of the patients that were significantly more frequent in the prolgolimab-combination group were blood creatinine increased and dyspnoea. Among patients with advanced NSCLC the addition of prolgolimab to pemetrexed and a platinum-based drug increased OS and PFS, with no new safety concerns. This benefit was retained in patients with PD-L1 negative tumors. (ClinicalTrials.gov, NCT03912389) •Significant benefits in overall survival and progression free survival•OS and PFS benefits are retained in PD-L1 TPS