Preliminary Results Promising for Opdivo-Yervoy as First-Line in Advanced NSCLC

With a new dosing schedule, low toxicity and a PD-L1 expression-driven response was observed.

Data presented at the 16th World Conference on Lung Cancer by Bristol-Myers Squibb (BMS) provided an update on the ongoing phase 1b CheckMate-012 trial evaluating nivolumab as first-line treatment in chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC). Nivolumab has an FDA approval for the treatment of patients with metastatic squamous-cell NSCLC that progressed on or after treatment with platinum-based chemotherapy. Additionally, an application for the drug in previously-treated patients with metastatic nonsquamous cell NSCLC was granted a priority review by the FDA, with an expected action date of January 2, 2016.

According to the associated press release, nivolumab was administered as monotherapy or in combination with other agents, including ipilimumab, at different doses and schedules. The updated results included data from 4 novel dosing schedules in 148 patients (both squamous and non-squamous) treated with nivolumab plus ipilimumab that yielded objective response rates in the range of 13% to 39%. While the median progression-free survival ranged between 4.9 months and 10.6 months, median duration of response had not been achieved in any of the arms during a median follow-up period that ranged from 6.2 months to 16.6 months.

Overall, treatment-related serious adverse events mirrored those previously reported from the nivolumab plus ipilimumab cohorts in Checkmate-012. BMS claims that the new dosing schedules reduced drug toxicity and treatment-related adverse events resulting in discontinuation.

“The preliminary results from this trial in advanced non-small cell lung cancer similarly push the envelope of benefit with an immunotherapy combination strategy in the first-line treatment of advanced non-small cell lung cancer which warrants further studies,” lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center.

The trial also evaluated the PD-L1-driven efficacy of the combination of nivolumab and ipilimumab. While the 2-drug regimen showed clinical activity in expressors as well as nonexpressors, PD-L1 expressing subjects responded better.