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The ongoing phase 3 CheckMate -227 study met its co-primary endpoint of progression-free survival ( PFS ) with the Opdivo ( Nivolumab ) plus Yervoy ( Ipilimumab ) combination versus chemotherapy in first-line advanced non-small cell lung cancer ( NSCLC ) patients whose tumors have high ( greater than or equal to 10 mutations/megabase [ mut/mb ] ) tumor mutation burden ( TMB ), regardless of PD-L1 expression.

In the study, TMB was evaluated using assay FoundationOne CDx.

Additionally, based on an interim analysis for overall survival ( OS ), the Data Monitoring Committee recommended that the study continue.

The safety profile was consistent with previously reported findings in first-line NSCLC for the combination schedule of Nivolumab 3 mg/kg every two weeks and low-dose Ipilimumab ( 1 mg/kg ) every six weeks.

CheckMate -227 is an open-label phase 3 trial with more than 2,500 patients randomized across non-squamous and squamous histologies, evaluating Nivolumab-based regimens versus Platinum-doublet chemotherapy in patients with first-line advanced non-small cell lung cancer.
This large program is comprised of three parts: Parts 1a and 1b and Part 2.

Part 1a is evaluating Nivolumab plus Ipilimumab and Nivolumab monotherapy versus chemotherapy in patients whose tumors express PD-L1.
Part 1b evaluated Nivolumab plus Ipilimumab and Nivolumab plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1.
PD-L1 expression levels were assessed using the Dako-developed diagnostic PD-L1 IHC 28-8 pharmDx.
Part 2 is evaluating Nivolumab plus chemotherapy versus chemotherapy in a broad population with a primary endpoint of overall survival.

Nivolumab and Ipilimumab are dosed as follows in the study: Nivolumab 3 mg/kg every two weeks with low-dose Ipilimumab ( 1 mg/kg ) every six weeks.

The result is based on an analysis of patients from the Nivolumab plus Ipilimumab arms and chemotherapy arms across all of Part 1.
There are two co-primary endpoints in Part 1 for the Nivolumab plus Ipilimumab combination: overall survival in patients whose tumors express PD-L1 ( assessed in patients enrolled in Part 1a ) and progression-free survival in patients with high tumor mutation burden, regardless of PD-L1 expression ( assessed in patients enrolled across Parts 1a and 1b ).
Approximately 45% of the TMB-evaluable patients had tumors that expressed high ( greater than or equal to 10 mut/mb ) TMB in the study.

Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutation burden, or TMB, is a quantitative biomarker that reflects the total number of mutations carried by tumor cells.
Tumor cells with high TMB have higher levels of neoantigens, which are thought to help the immune system recognize tumors and incite an increase in cancer-fighting T cells and an anti-tumor response.
TMB is one type of biomarker that may help predict the likelihood a patient responds to immunotherapies. ( Xagena )

Source: BMS, 2018

XagenaMedicine2018