New Study Shows Nivolumab and Ipilimumab Combination Therapy is Effective for Non-Small Cell Lung Cancer Patients, Say Moffitt Researchers

December 05, 2016

TAMPA, Fla. – Lung cancer is the number one cause of cancer-related mortality in the United States, with over 158,000 deaths each year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, affecting approximately 85 percent of lung cancer patients.  There is an urgent need to identify better initial treatment options for NSCLC to reduce the high mortality rate of this disease. Researchers from Moffitt Cancer Center and several collaborative institutions published study results today in The Lancet Oncology showing that the drug combination nivolumab and ipilimumab may be an effective initial treatment option for patients with advanced NSCLC.

Significant strides have been made in recent years in regard to understanding the role of the immune system in tumor development. Tumors can harness the properties of the immune system to avoid detection and continue to grow and spread. Nivolumab and ipilimumab are two drugs that have been approved by the Food and Drug Administration to reactivate the immune system to recognize tumor cells and target them for destruction. 

Nivolumab inhibits a protein called PD-1 and is approved to treat several different malignancies, including advanced NSCLC patients who were previously treated with a standard chemotherapy regimen.  Ipilimumab inhibits a protein called CTLA-4 and is approved to treat advanced metastatic melanoma. Recently, the combination of nivolumab and ipilimumab was also approved for advanced metastatic melanoma based on data showing that the combination resulted in a 60 percent reduced risk of progression or death when compared to either drug alone.

In order to determine if the combination is also more effective in advanced NSCLC patients, the phase 1 CheckMate 012 trial was initiated.  The trial was conducted at twelve cancer centers throughout the United States and Canada, including Moffitt. The goal of the study was to determine the safety and clinical activity of nivolumab plus ipilimumab in previously untreated patients with advanced NSCLC.

Previously published data from the CheckMate 012 study suggested that higher doses of both nivolumab and ipilimumab were intolerable to NSCLC patients.  Fifty-one percent of the patients experienced high-grade adverse events and more than 30 percent of patients had to discontinue treatment because of these toxicities. In the current publication, the researchers report additional results from the CheckMate 012 study from 77 NSCLC patients who were treated with lower drug concentrations and less frequently.


The patients were treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg given either every 12 weeks (Q12W) or every 6 weeks (Q6W). The researchers report that both treatment schedules were less toxic and fewer patients discontinued treatment because of toxicities than the previously reported treatment schedules. High-grade toxicities occurred in 37 percent of the patients on the Q12W schedule and in 33 percent of patients on the Q6W schedule. The most common high-grade toxicities were altered pancreas activity, pneumonitis, altered adrenal gland activity, and colitis.

The researchers also report that both treatment schedules were active in NSCLC patients, with 47 percent of patients in the Q12W group achieving a response and 38 percent of the patients in the Q6W group achieving a response. The majority of these responses were durable. Over 70% of patients maintained their response for an extended period of time in both treatment groups.  Importantly, the researchers determined that the nivolumab and ipilimumab combination was highly active in patients who had tumor expression of the PD-L1 protein, with 57 percent of these patients achieving a response.

These results in NSCLC are encouraging and an ongoing phase 3 clinical trial is currently comparing the efficacy of the combination of nivolumab and ipilimumab to either nivolumab alone or standard chemotherapy in previously untreated advanced NSCLC patients.

The study was funded by Bristol-Myers Squibb, makers of nivolumab and ipilimumab.

About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 47 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, clinical trials, prevention and cancer control. Moffitt is the No. 6 cancer hospital in the nation and has been listed in U.S. News & World Report as one of the “Best Hospitals” for cancer care since 1999. Moffitt devotes more than 2.5 million square feet to research and patient care. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 5,200 team members, Moffitt has an economic impact in the state of $2.1 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit, and follow the momentum on Facebook, Twitter and YouTube