Nivolumab Receives Priority Review for NSCLC

The FDA has granted a priority review to nivolumab (Opdivo) for use in patients with previously treated, advanced, squamous non—small cell lung cancer (NSCLC), according to Bristol-Myers Squibb (BMS), the company that manufactures the anti–PD-1 agent. Under the expedited review, the FDA will make a final approval decision by June 22, 2015.

The priority designation is based on data from the open-label, single-arm, phase II CheckMate-063 study, in which treatment with nivolumab produced an overall response rate (ORR) of 15% in patients with advanced, squamous NSCLC. The estimated 1-year survival rate was 41%.

“With the acceptance of our application for Opdivo in the squamous non—small cell lung cancer setting, Bristol-Myers Squibb marks another significant milestone in its goal to deliver a new treatment option for this challenging to treat patient population,” said Michael Giordano, MD, senior vice president, Head of Oncology Development, at BMS.

Data from the CheckMate-063 were presented at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. The trial included 117 heavily pretreated patients with advanced squamous cell NSCLC. All patients had failed two or more systemic treatments and 65% of participants (n = 76) had previously failed three or more treatments. Seventy-six percent of patients were within 3 months of completion of their most recent therapy.

Patients received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or treatment discontinuation.

At 11 months’ follow-up ORR, as assessed by an independent panel, was 15% (95% CI, 8.7-22.2), with a median duration of response that was not yet reached.

The estimated 1-year survival rate was 41% (95% CI, 31.6-49.7) and the median overall survival (OS) was 8.2 months (95% CI, 6.05-0.91).

An additional 26% of patients had stable disease for a median duration of 6 months (95% CI, 4.73-10.91), producing a disease control rate (ORR plus stable disease) of 41%. Responses were observed independent of PD-L1 status for patients with quantifiable PD-L1 expression.

“There are currently no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two prior therapies. Historically, these patients have had ORRs of 2% to 8% and median overall survival of about 5 months, so even though we have not yet reached the median duration of response [in this study], the signs are very promising,” said lead author Suresh S. Ramalingam, MD, when he presented the data in Chicago.

Ramalingam, who is a professor and director of medical oncology at Winship Cancer Institute of Emory University, added that the 41% 1-year OS rate compares favorably with previously demonstrated 1-year survival rates of 5.5% to 18% for patients with third-line squamous cell NSCLC.

Adverse events (AEs) of all types and grades occurred in 74% of patients; however, 85% of patients were able to receive at least 90% of their planned dose intensity.

Grade 3/4 drug-related AEs were reported in 17% of patients. The most common (≥2%) grade 3/4 AEs were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%).

Discontinuations due to drug-related AEs of any grade occurred in 12% of patients.

Two drug-related deaths (1 hypoxic pneumonia, 1 ischemic stroke) occurred in patients with multiple comorbidities and progressive disease.

Earlier this year, BMS announced that nivolumab improved survival versus docetaxel in patients with pretreated squamous cell NSCLC in the phase III CheckMate-017 trial.

The open-label CheckMate-017 study involved 272 previously treated patients with advanced or metastatic squamous cell NSCLC. Participants were randomized to the fully human IgG4 monoclonal antibody nivolumab at 3 mg/kg intravenously every 2 weeks or docetaxel at 75 mg/m² intravenously every 3 weeks.

The study was stopped early after an independent monitoring panel determined the primary endpoint of improved OS with the anti—PD-1 agent had been reached. Eligible patients were allowed to continue treatment or cross over to the nivolumab arm in an open-label extension of CheckMate-017.

BMS is working with the researchers on a timetable for publication and presentation of the study data.

“As a company that prides itself in helping patients prevail over deadly diseases, we are proud of this achievement and look forward to making Opdivo available to the lung cancer community,” said Giordano.

Nivolumab was approved by the FDA in December 2014 for patients with unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor.