From protocol 4.0, the randomization is 2:1. Patients should be treated as soon as possible with the allocated treatment, and preferably within 15 days after randomization. 4.6 Study Endpoints 4.6.1 Efficacy endpoints Primary efficacy endpoint : • OS: OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 50 of 101 02 February 2022 o In Step 1: OS rate at 12 months in experimental Arm A (OSE2101) in 84 evaluable patients exposed to OSE2101 o In Step 2: comparison of OS betw een experimental Arm A (OSE2101) and control Arm B (docetaxel or pemetrexed) when 278 events observed ; due to early study discontinuation (219 patients included instead of 363 patients), statistical hypothesis was revised with a comparison between experime ntal Arm A and control Arm B in the PoI (refer statistical methodology section) Secondary efficacy endpoints (in Steps 1 & 2) : • DCR at 6 and 12 months based on RECIST 1.1 • QLQ -C30 (EORTC QLQ questionna ire): “Global health status/QoL” score based on questions 29 (How would you rate your overall health during the past week? ) and 30 (How would you rate your overall quality of life during the past week? ) (in Step 1 only) • QLQ -LC13 (lung cancer module from EORTC QLQ questionnaire): time to 1st ≥ 10 - point det erioration in chest pain score (question 40) , dyspnea score (question 33, 34, 35) or cough score (question 31) (in Step 1 only ) • Post Progression Survival • Time to worsening of ECOG PS • QLQ -C30 Global health status score change from baseline (in Step 2 only) • QLQ -C30 Functional scores change from baseline (in Step 2 only) • QLQ -C30 Symptom scores change from baseline (in Step 2 only) • QLQ -LC13 Symptom scores change from baseline (in Step 2 only • PFS based on RECIST1.1 • ORR (in Step 1 only) • DR (in Step 1 only) Exploratory efficacy endpoints : In Step 2 only: • ORR • DR • All the other scores of QoL • COVID -19 impact In Steps 1: • TTD in patient reported chest pain • TTD in patient reported dyspnea • TTD in patient reported cough In Steps 1 & 2: • Time to next lung cancer therapy 4.6.2 Safety and tolerability endpoints • Incidence, severity, seriousness and relationship to study treatments of adverse events (AE) and immune -related adverse events (irAE) and any laboratory abnormalities . OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 51 of 101 02 February 2022 4.6.3 Exploratory translational endpoints Patients who agreed to participate in this exploratory translational study , will have to sign a specific inform consent.