8.9. Concomitant Medications A concomitant medication is defined as any medication taken on or after the day of first exposure to study drug up until 28 days after last dose of study drug. Prior medic ations are defined as any medication that is taken prior to the day of first exposure to any study drug. The number and percentages of all concomitant medications will be summarized on the ITT sets and by treatment arm, Anatomical Therapeutic Chemical (ATC ) level 1 (sorted according to the corresponding first letter of the 5-digit ATC code) , and Preferred Term. The number and percentages of subjects with at least one concomitant medication will be summarized by treatment arm. Medications received for the d isease after stopping study drug will summarized on the ITT sets by treatment arm using the same presentation. The total number of concomitant medications present at baseline (day of first exposure to study) and the corresponding number and percentages of subjects will also be summarized by treatment arm. Since treatment received for the disease after stopping drug is not limited to medications (it includes radiotherapy), the text ‘ Medications received for the disease after stopping study dru g will summarized on the ITT sets by treatment arm using the same presentation. ’ should be changed to ‘Treatments received for the disease after stopping study drug will be summarized on the Safety set by treatment arm using the presentation (using ATC lev el 1 and PT for medications and SOC and PT for non -drug treatments)’. 8.10. Treatment Compliance The number of days between first and last exposure to treatment up to the analysis cut -off date , the total administered dose up to the analysis cut -off date and the corresponding dose intensity – calculated as total administered dose as a proportion of total planned dose – will be summarized by treatment arm for the Safety sets. The total dose will be reported separately for each of the two treatments in arm B (doceta xel, pemetrexed). The descriptive statistics of the number of cycles where the study drug was administered received up to the analysis cut -off date will be summarized by treatment arm. OSE Immunotherapeutics v2.2 Study OSE2101C301 (ATALANTE 1) Statistical Analysis Plan 2021 -07-23 IND#: BB-IND 10802 CONFIDENTIAL P a g e | 33/51 8.11. Time Intervals 8.11.1. Time Intervals between Cycles Descriptive statistics by treatment arm of the number of weeks between Cycle 1 Day 1 and the randomization and then between each of the other Cycle Day 1 visits and the preceding Cycle Day 1 visit will be presented by treatment arm on the ITT sets. Cycles performed after the analys is cut -off date will be ignored. Patients with a cycle delayed more than 7 days after the theoretical date defined for the treatment arm will be listed. Cycles taken into account will be those with a study drug administration recorded. 8.11.2. Survival Data Collected on the Censored Patients and Duration of Follow - up Descriptive statistics by treatment arm of the weeks since randomization and days between last survival information and date of database extraction will be prepared on the censored patients (excl uding withdrawals of consent) for the ITT sets. For patients with survival information collected after the analysis cut -off date witnessing that they were alive at the time of the cut - off date, weeks since randomization are counted to the cut -off date and days between last survival information and date of database extraction is counted as 0 days. Duration of Follow -up will be presented using reverse Kaplan Meier methodology. This method is calculated in the same way as the Kaplan -Meier estimate of the survival function, but with the meaning of the status indicator reversed so that our event of interest becomes the censor, and the censor becomes event. 8.11.3. Time Intervals between RECIST Assessments Descriptive statistics by treatment arm of the number o f weeks between the first post-baseline RECIST assessment and the randomization and then between each of the other post-baseline RECIST assessments and the preceding assessment will be presented on the ITT set. Assessments performed after the analysis cut -off date will be ignored. 8.11.4. Time Intervals between Quality of Life Assessments Descriptive statistics by treatment arm of the number of weeks between the first post -baseline QOL questionnaire and the randomization and then between each of the other post -baseline QOL questionnaires and the preceding QOL questionnaire will be presented on the ITT set. Questionnaires completed after the analysis cut -off date will be ignored. OSE Immunotherapeutics v2.2 Study OSE2101C301 (ATALANTE 1) Statistical Analysis Plan 2021 -07-23 IND#: BB-IND 10802 CONFIDENTIAL P a g e | 34/51 9. EFFICACY ANALYSES Unless otherwise noted, all efficacy analyses will be completed using the ITT sets and in PP sets only for primary endpoint analyses . All efficacy analyses will be completed using the treatment arms as assigned by the randomization . 9.1. Overall Survival (OS) For the ITT sets, OS is defined as time from randomization to death , expressed in months , will be censored at the analysis cut-off date (15JAN2021) . For instance, a patient with last news = alive after the cut -off date will be censored at the cut -off date , a patient with death after the cut-off date be counted as alive (but censored ) at the cut -off date . [Note to programmers: the OS time and censoring flag derived without using the analysis cut -off date will also be derived and kept as supplementary records in the ADTTE ADaM dataset] OS will be summarized using the Kaplan -Meier method and displayed graphically. The median and Q1, Q3 event time s for each treatment arm and the corresponding 2 -sided 95% confidence interval will be provid ed. A 2-sided log -rank test stratified for the randomization stratification factors will be used to compare OS between the two treatment arms. The Cox regression model, stratified for the same stratification factors, will be fitted, and the estimated hazar d ratio and 2 -sided 95% confidence int erval will be provided. The hazard ratio, as estimated in this Cox regression model, will be provided with its 2 -sided 95% CI on the Kaplan -Meier plot. A two-sided unstratified log -rank test and an unstratified Cox reg ression model will also be used as additional secondary analyses for OS. The six -month survival rate will be estimated using the Kaplan -Meier method and a 2 -sided 95% confidence interval for the log [ -log(6 -months survival probability)] will be calculated using a normal approximation and then back transformed to give a confidence interval for the 6-months survival rate itself. The 12 -month survival rate will be estimated similarly. These analyses will be implemented by the following example SAS® code: Log-rank test stratified : proc lifetest ; strata factor1 factor2 factor3 / group= trt; time time*cnsr( 1); run; Log-rank test unstratified : proc lifetest ; OSE Immunotherapeutics v2.2 Study OSE2101C301 (ATALANTE 1) Statistical Analysis Plan 2021 -07-23 IND#: BB-IND 10802 CONFIDENTIAL P a g e | 35/51 strata trt; time time*cnsr( 1); run; Cox model stratified : proc phreg; class trt(ref="1");*1 = control group; model time*cnsr( 1) = trt / ties=exact rl; strata factor1 factor2 factor3; run; Cox model unstratified : proc phreg; class trt(ref="1");*1 = control group; model time*cnsr( 1) = trt / ties=exact rl; run; NB: ties=exact may be replaced by ties=efron in case of calculation issues . All survival analyses described above will be repeated on the PP set (OS). Subgroups analyses of OS will be performed on the ITT sets to determine whether treatment effect is consistent among subgroups . More specifically, results of the subgroup analyses will be displayed in a forest plot including: • For each subgroup level, the number of events, the sa mple size, the median survival time (months) and the estimate of the treatment effect (HR) with its 95% confidence interval as obtained for a separate unstratified and stratified Cox model within each subgroup level. • The logarithmic scale used to graphically represent the treatment effect estimates and their 95% confidence interval will be restricted to 0.20 - 5.00 (a few confidence intervals may overflow these limits). • A p-value for the interaction test obtained from the unstratified Cox model including terms for “subgroup”, “treatment”, “treatment by subgroup” interaction. • A vertical reference line displayed at the level of the overall treatment effect. • The subgroup analysis will not be performed in subgroups with les s than 10 patients (for variables with more than 2 levels, the level with the sample size below 10 may be collapsed with one of the adjacent levels, if appropriate). Additionally, multivariate Cox regression model s, stratified for the same stratification f actors as used for the randomization, will be used on the ITT set s to explore the potential joint influences of the other factors (those defining subgroups in the text above) on the primary OS endpoint. If deemed appropriate backward selection of variables will be used. The results of the subgroup analyses will be detailed in a summary table and summarized in a forest plot. The forest plot will present for each subgroup variable the p -value of the interaction test and for within each subgroup level the samp le size by treatment arm, the median survival OSE Immunotherapeutics v2.2 Study OSE2101C301 (ATALANTE 1) Statistical Analysis Plan 2021 -07-23 IND#: BB-IND 10802 CONFIDENTIAL P a g e | 36/51 time (months) by treatment arm with is 95% confidence interval , the HR with is 95% confidence interval. Same information will be provided in the Figures presenting the Kaplan - Meier curves.