Opdivo Receives Priority Review for Non-Small Cell Lung Cancer

The Food and Drug Administration (FDA) has granted a priority review to Opdivo (nivolumab) 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 2 CheckMate-063 study, in which treatment with Opdivo produced an overall response rate (ORR) of 15 percent in patients with advanced, squamous NSCLC. The estimated 1-year survival rate was 41 percent.

“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,” says 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 percent of participants 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 Opdivo 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 percent, with a median duration of response that was not yet reached. The estimated 1-year survival rate was 41 percent and the median overall survival (OS) was 8.2 months.

An additional 26 percent of patients had stable disease for a median duration of 6 months, producing a disease control rate (ORR plus stable disease) of 41 percent. 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 percent to 8 percent and median overall survival of about five months, so even though we have not yet reached the median duration of response [in this study], the signs are very promising,” says 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 percent 1-year OS rate compares favorably with previously demonstrated 1-year survival rates of 5.5percent to 18 percent for patients with third-line squamous cell NSCLC.

Adverse events (AEs) of all types and grades occurred in 74 percent of patients; however, 85 percent of patients were able to receive at least 90 percent of their planned dose intensity. Grade 3/4 drug-related AEs were reported in 17 percent of patients. The most common were fatigue, pneumonitis and diarrhea.

Earlier this year, BMS announced that Opdivo improved survival versus docetaxel in patients with pretreated squamous cell non—small cell lung cancer (NSCLC) in the phase 3 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 Opdivo 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 Opdivo 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. Opdivo was approved by the FDA in December 2014 for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor.