Trial Outcomes & Findings for Safety and Efficacy Study of CC-486 With MK-3475 to Treat Locally Advanced or Metastatic Non-small Cell Lung Cancer (NCT NCT02546986)

This study was a multicenter study with 25 sites from the United States, France. Germany, Italy, and Spain.

Qualified participants were randomized in a 1:1 ratio to one of the two treatment groups. Randomization was stratified by cancer histology (non-squamous versus squamous).

The Intent-to-Treat population includes all participants who were randomized.

PFS was defined according to the FDA Methodology as the time in months from the date of randomization to the date of disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (documented by computed tomography scan, not including symptomatic deterioration) or death for (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment where the participant was documented to be progression-free prior to the data cutoff date. Progressive disease includes at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion.

Progression-free survival was defined according to EMA methodology as the time from the date of randomization to the date of disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (documented by computed tomography scan result, not including symptomatic deterioration) or death for (any cause) on or prior to the data cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. However, occasional missing observations or initiation of subsequent new anticancer therapy would not result in censoring for this analysis. Progressive disease is at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion.

Disease control rate was defined as the percentage of participants who had confirmed stable disease, complete or partial response during the course of study, according to RECIST v1.1, as evaluated by the investigator. RECIST v 1.1 is defined as: - Complete response: disappearance of all target lesions - Partial response: at least a 30% decrease in the sum of diameters of target lesions from baseline - Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease - Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion. When stable disease was believed to be the best response, it must have met the minimum duration of 10 weeks from randomization.

Overall survival (OS) was defined as the time in months between day 1 of treatment and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off, whichever was earlier. Participants who were lost to follow-up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact.

The best overall response is defined as the percentage of participants who achieved an objective confirmed complete response or partial response according to RECIST v1.1, compared with baseline where baseline was the last computed tomography (CT) scan obtained prior to or on day 1 of study treatment. RECIST v1.1 is defined as: - Complete response: disappearance of all target lesions - Partial response: at least a 30% decrease in the sum of diameters of target lesions from baseline - Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease - Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion.

Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild; Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.

Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/ λz\]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC % extrap is ≥25%, AUCi inf was not reported.

Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.

Terminal phase half-life in plasma, calculated as \[(ln 2)/λz\]. t1/2 was only be calculated when a reliable estimate for λz could be obtained.

Apparent total plasma clearance (CL/F) of CC-486 was calculated as Dose/AUC∞

Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz