Safety was consistent with previous reports of 1L nivo + ipi for this dose regimen.
![checkmate 227 checkmate 227](http://img.cn.cphi.cn/img_Cphi_cn/news/2020_05/Mimg_2005171107651244.png)
Part 1 continues for final OS in the PD-L1-selected co-primary population.Ĭonclusions: CheckMate 227 met its co-primary endpoint of significantly prolonged PFS with 1L nivo + ipi vs PT-DC in NSCLC with TMB ≥10 mut/Mb regardless of PD-L1 expression. In treated pts, grade 3-4 treatment-related adverse events rates were 31.3% and 36.1% with nivo + ipi and PT-DC, respectively. Objective response rate was 45.3% with nivo + ipi vs 26.9% with PT-DC in pts with TMB ≥10 mut/Mb median duration of response (95% CI) was not reached (12.2 mo, NR) vs 5.4 (4.2, 6.9) mo, respectively. In all randomized pts, the HR for PFS with nivo + ipi vs PT-DC was 0.83 (95% CI: 0.72, 0.96). PFS was significantly longer with nivo + ipi vs PT-DC in pts with TMB ≥10 mut/Mb (HR=0.58 P=0.0002) results were broadly consistent across subgroups, including PD-L1 and histology. Results: Baseline characteristics were similar in pts with evaluable TMB and all randomized pts and were balanced between nivo + ipi and PT-DC arms. Co-primary endpoints were overall survival (OS) for nivo + ipi vs PT-DC in pts with PD-L1-selected tumors and PFS (blinded independent central review) for nivo + ipi vs PT-DC in pts with TMB ≥10 mutations (mut)/Mb. TMB was determined from tumor tissue using the validated FoundationOne CDx™ assay (Foundation Medicine, Inc.). Pts were treated until disease progression or unacceptable toxicity, up to 2 y. Tx regimens were nivo 3 mg/kg Q2W + ipi 1 mg/kg Q6W, nivo 240 mg Q2W, or nivo 360 mg Q3W with PT-DC. Pts with ≥1% tumor PD-L1 expression were randomized 1:1:1 to nivo + ipi, nivo, or PT-DC pts with <1% tumor PD-L1 expression were randomized 1:1:1 to nivo + ipi, nivo + PT-DC, or PT-DC. Methods: Patients (pts N=1739) with chemotherapy-naive, histologically confirmed stage IV or recurrent NSCLC, ECOG PS 0−1, and no known sensitizing EGFR/ALK mutations were enrolled in 2 groups: PD-L1 ≥1% or PD-L1 <1%. We report initial results from Part 1 of the study. This is the first phase 3 study to evaluate TMB as a predictive biomarker for immunotherapy as a co-primary endpoint. A preplanned co-primary endpoint was based on TMB to evaluate progression-free survival (PFS) of nivo + ipi vs PT-DC. CheckMate 227 (NCT02477826) is a large, open-label, phase 3 study of 1L nivo + ipi, nivo, or nivo + PT-DC vs PT-DC in advanced NSCLC. Tumor mutation burden (TMB) has emerged as an important biomarker for benefit of immune checkpoint blockade in lung cancer. Background: Nivo + ipi showed promising clinical activity and tolerability as 1L tx for advanced NSCLC in a phase 1 study.