The combination of nivolumab with low dose ipilimumab reduces the risk of developing disease or death by 42% compared to chemotherapy in front-line patients with lung cancer and high tumor burden mutations (TMB), according to the initial results from the baseline Phase study 3 CheckMate-227 presented at the annual AACR conference in Chicago.
In particular, the study looked at the combination of nivolumab 3 mg / kg with 1 mg / kg ipilimumab as the first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) and high volume mutations (TMB) ≥ 10 mutations / (mut / Mb).
In the study, the combination showed a superior benefit with regard to the co-primary endpoint of non-progression-free survival (PFS) versus chemotherapy (HR 0.58, 97.5% CI: 0.41 to 0.81, p = 0.0002). The benefit for PFS was observed regardless of PD-L1 expression levels, as well as in both histological types of squamous and non-squamous cells.
In addition, based on an early descriptive analysis, encouraging overall survival by combination with chemotherapy was observed in patients with high TMB ≥10 mut / Mb (HR 0.79, 95% CI: 0.56 to 1.10).
Grade 3-4 adverse events (AE) associated with treatment were cutaneous reactions (34%), endocrine events (23%), gastrointestinal events (18%), hepatic events (15%), respiratory (8%), hypersensitivity (4%) and renal events (4%). Overall, treatment-related deaths occurred in 1% of patients treated in the combination and chemotherapy arms.
“CheckMate-227 is the first Phase 3 study demonstrating the significant clinical benefit of combining two immunotherapeutic agents for the first-line treatment of patients with NSCLC and high TMB. The results showed that first-line treatment with nivolumab and ipilimumab may provide responses with increased duration, depth and frequency compared to chemotherapy in patients with NSCLC who have TMB ≥10 mut / Mb.
The study also supports the rationale for conducting molecular testing to determine potential biological markers in lung cancer patients, “said Matthew Helman, a study investigator oncologist at the Memorial Sloan Kettering Cancer Center.