FDA Approves Frontline Nivolumab Plus Ipilimumab for Metastatic NSCLC

The FDA approved nivolumab (Opdivo) plus ipilimumab (Yervoy) for the frontline treatment of patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with no EGFR or ALK aberrations.

The approval was based on data from the multi-part, open-label phase III CheckMate-227 trial, which examined the 2-drug combination compared to chemotherapy in patients with previously untreated NSCLC. Researchers evaluated 2 arms in part 1 of the trial:

Nivolumab plus low-dose ipilimumab or nivolumab alone versus chemotherapy in patients whose tumors express PD-L1 (part 1a)

Nivolumab plus low-dose ipilimumab plus chemotherapy versus chemotherapy alone in patients whose tumors express PD-L1 (part 1b)

Primary endpoints were overall survival (OS) in patients whose tumors expressed PD-L1, as well as progression-free survival (PFS) in patient’s tumor mutation burden (TMB) of 10 mut/Mb or higher across the PD-L1 spectrum. Median OS for the combination compared to chemotherapy was 17.1 months and 14.9 months, respectively. OS was 17.1 months with the combination and 13.9 months with chemotherapy in all patients regardless of PD-L1 expression.

Median duration of response by blinded independent central review was 23.2 months, 15.5 months, and 6.2 months for the combo, nivolumab alone, and chemotherapy, respectively. At 1 year, the percentage of patients in response were 64%, 63%, and 28%; at 2 years, it was 49%, 40%, and 11% respectively.

For all randomized patients, regardless of PD-L1 expression status, the 1-year OS rates with nivolumab/ipilimumab and chemotherapy were 62% and 54%, respectively; the 2-year OS rates were 40% and 30%, respectively.

There were no new safety findings of the combination reported with longer follow-up in part 1. Grade 3/4 treatment-related adverse events were reported in 32.8%, 19%, and 36.0% of patients in the nivolumab/ipilimumab, single-agent nivolumab, and chemotherapy arms, respectively.