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
FSBI "N.N. Blokhin National Medical Research Center of Oncology" of the Russian Ministry of Health, Moscow, Russia.
FSBI "Academician N.N. Burdenko Main Military Clinical Hospital", MoH, Moscow, Russia.
Eur J Cancer. 2025 Feb 25;217:115255. doi: 10.1016/j.ejca.2025.115255. Epub 2025 Jan 21.
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).
普罗戈利单抗是一种具有Fc沉默“LALA”突变的IgG1抗PD - 1单克隆抗体。III期DOMAJOR研究评估了普罗戈利单抗联合培美曲塞和铂类化疗与安慰剂联合培美曲塞和铂类化疗作为晚期非小细胞肺癌（NSCLC）一线治疗的疗效和安全性。
292例晚期非鳞状NSCLC患者按1:1随机分组，接受4个周期的培美曲塞、铂类药物，以及普罗戈利单抗（3 mg/kg，每3周一次）或安慰剂，随后接受普罗戈利单抗/安慰剂联合培美曲塞治疗，直至疾病进展或出现毒性（≤36个月）。主要终点是总生存期（OS）。
中位随访18个月后，普罗戈利单抗联合治疗组未达到中位OS（95%CI，22.28 - 未达到），而安慰剂联合治疗组为14.6个月（95%CI，11.73 - 19.15）（风险比[HR]，0.51；95%CI，0.35 - 0.73，p = 0.00
