Prolgolimab with chemotherapy as eerstelijns treatment for gevorderd non-squamous non-small-cell lung cancer.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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).