(Lung Cancer) High Tumor Mutational Burden (TMB) and Its Association with NSCLC Treatment

High tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC) patients receiving first-line combination Opdivo (nivolumab) and Yervoy (ipilimumab) was associated with a statistically significant improvement in progression-free survival (PFS).

On February 5, 2018, Ono Pharmaceutical announced the Phase III clinical trial results of CheckMate-227 (NCT02477826), which evaluated first-line treatment combining Yervoy and Opdivo in NSCLC patients.

The CheckMate-227 trial enrolled over 2,500 NSCLC patients and was divided into three parts based on PD-L1 positive, PD-L1 negative, and broader patient background data.

For PD-L1-positive patients: the groups were Opdivo monotherapy, Opdivo + Yervoy combination, and chemotherapy; and Opdivo + chemotherapy combination (Part 1a). For PD-L1-negative patients, the same groupings minus Opdivo monotherapy were used (Part 1b).

The data reported this time focused on patients with high TMB regardless of PD-L1 status, comparing biweekly Opdivo 3 mg/kg + every-six-week Yervoy 1 mg/kg with chemotherapy using PFS as the comparative analysis metric.

TMB was assessed using Foundation Medicine's Foundation One CDx. Among the enrolled patients, 45% had tumor mutational burden ≥10 mut/Mb.

The primary endpoint PFS analysis showed that statistically, the combination of the two drugs was proven to extend PFS.

Based on CheckMate-227 data, Dr. Matthew D. Hellmann stated: Through this trial, the total genomic tumor mutation load — tumor mutational burden (TMB) — was demonstrated to be a biomarker that can indicate immunotherapy activity. Regardless of PD-L1 status, when using Opdivo + Yervoy, TMB can serve as a reference indicator.

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