Nivolumab in Chemotherapy-Naïve Advanced NSCLC

Conference Correspondent - ASCO 2014 - Immuno-Oncology

Nivolumab (NIV), a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has demonstrated durable responses and tolerability in patients with previously treated advanced non-small-cell lung cancer (NSCLC). In their updated analysis of a phase 1 trial of NIV in patients with previously treated NSCLC, Brahmer and colleagues reported median overall survival (OS) ranging from 9.2 to 14.9 months across NIV doses and NSCLC histologies. One- and 2-year OS rates were 42% and 24%, respectively, across NIV doses in patients with relapsed NSCLC (ASCO 2014; Abstract 8112).

On the basis of these findings, a phase 1 trial of NIV in patients with chemotherapy-naïve advanced NSCLC was undertaken. Gettinger and colleagues shared interim results of this trial, which enrolled patients with squamous or nonsquamous advanced NSCLC (ASCO 2014; Abstract 8024). Patients received NIV (3 mg/kg every 2 weeks) until progression or unacceptable toxicity. (Postprogression treatment was allowed based on protocol-defined criteria.) Data for NIV in the first 20 patients were reported. 

After 6 or more months of follow-up, 17 patients (85%) experienced treatment-related adverse events (AEs) of any grade. Grade 3/4 treatment-related AEs included elevations of liver enzymes, hyperglycemia, and rash. Pneumonitis (of any grade) was not observed.

The objective response rate (ORR) associated with NIV in these 20 patients was 30%, with 5 of 6 responders (83%) achieving response at the time of the first scan (week 11). Responses are durable and ongoing for all 5 patients; median duration of response (mDOR) has not been reached. 

Of 15 evaluable tumor samples, 9 expressed PD-L1. The ORR was 67% in PD-L1-positive patients, in contrast to no responses observed in the 6 PD-L1-negative patients (Table).


To date, this phase 1 study among chemotherapy-naïve patients with advanced NSCLC has demonstrated early and durable responses, as well as tolerability of NIV. These findings justify further study of NIV monotherapy in chemotherapy-naïve patients with advanced NSCLC.

Because PD-L1 status correlated with both ORR and progression-free survival (PFS), additional assessments of PD-L1 status are warranted. Follow-up findings and response data for 30 additional treated patients will be reported at subsequent meetings.