My name is Dr. Natasha Lael from the Princess Margaret Cancer Center, and on behalf of my colleagues, I'm delighted to present the results of the Checkmate 907 study, nivolumab given as flat dosing at 480 milligrams every four weeks for the de novo second line treatment of advanced non-small cell lung cancer. These are my disclosures. Nivolumab is the second line standard of care for immunotherapy naive patients with advanced non-small cell lung cancer, regardless of PD-L1 expression or histology. Pooled data from the randomized phase 3 Checkmate 017 and 057 studies demonstrate long-term benefit for weight-based dosing of nivolumab at 3 milligrams per kilogram every two weeks compared to dosotaxel with manageable safety. The overall response rate with nivolumab was 19.7%, the five-year survival 13.4%, and the rate of any great treatment-related adverse events was 67.9%. Benefit risk profile of nivolumab using 480 milligrams every four weeks as flat dosing is predicted to be similar to that of weight-based dosing using 3 milligrams per kilogram or flat dosing 240 milligrams every two weeks across multiple tumor types. Both of these flat dosing schedules are approved in the second line setting for lung cancer, and here we report the results of the phase 2 Checkmate 907 study evaluating the de novo administration of 480 milligrams of nivolumab every four weeks, a second-line treatment for immunotherapy naive patients with advanced non-small cell lung cancer. In the study, we enrolled 129 immunotherapy naive patients with either squamous or non-squamous histology. They must have had disease progression either during or after at least one systemic therapy and received prior EGFR inhibitor therapy if they had EGFR-activating mutations. Nivolumab 480 milligrams every four weeks was administered until disease progression, unacceptable toxicity, or up until two years. The primary endpoint was safety, specifically grade 3 and 4 or 5. Select treatment-related adverse events and efficacy endpoints were secondary. The minimum follow-up for this analysis was 26.5 months. Baseline characteristics are shown here and reflect a similar population as was enrolled in the Checkmate 017 and 057 studies, including predominance of men, 74%, white patients, 74%, smokers, 78%, 37% squamous, and 36% had PD-L1 negative disease. Safety was the primary endpoint of this study, and the results are consistent with this dosing schedule compared to weight-based 3 milligram per kilogram every two-week dosing. With a median of three months treatment duration, 67% of patients experienced a treatment-related adverse event, 5% of these were grade 3 or 4, and 2% of treatment-related adverse events that led to treatment discontinuation. There were no grade 5 toxicities or treatment-related deaths. Skin toxicity was the most commonly seen select adverse event occurring in 34% of patients, followed by hepatic, GI, endocrine, hypersensitivity or infusion-related reactions, and pulmonary events shown here. The median survival in this cohort was 10.6 months. One- and two-year survival rates were 46% and 25% respectively. For investigator-assessed progression-free survival, median PFS was 3.7 months, and the one- and two-year rates were 19% and 11%. These outcomes are similar to what we saw in the pooled Checkmate 017 and 057 studies with 3 milligram per kilogram every two-week dosing. The overall response rate was also similar, 17.1%, similar in both squamous and non-squamous subgroups, and 2% of patients had a complete response. The median duration of response was not reached, and 64% of responders remained in response at the time of database lock. The time to response was 3.6 months. The safety profile for the de novo administration of nivolumab 480 milligrams every four weeks was consistent with weight-based dosing from the Checkmate 017 and 057 analysis with no new safety signals. Most treatment-related select adverse events were low-grade, and efficacy outcomes were similar to what was seen in the registrational phase 3 trials. These results from Checkmate 907 support the de novo administration of nivolumab 480 milligrams every four weeks in multiple tumor types, including second-line advanced non-small cell lung cancer. We want to thank the patients and families who made this trial possible, all of the clinical study teams, and again, to thank all of the investigators and their sites. Thank you.

Dr. Natasha Lael

Checkmate 907 study

nivolumab

non-small cell lung cancer

immunotherapy naive patients