To confirm the superiority of OSE2101 versus docetaxel on Overall Survival (OS)

To confirm the clinical benefit of OSE2101 versus docetaxel including Patient Reported Outcomes (PROs)

HLA-A2 positive patients with squamous and non-squamous metastatic NSCLC who progressed after ≥ 24 weeks of first line CT-ICI, including at least 12-weeks of anti-PD(L)1 as monotherapy or in combination with another ICI prior to randomization

1. Patients expressing HLA-A2 phenotype in blood by pre-screening central laboratory 2. Patients with histologically or cytologically squamous or non-squamous documented NSCLC, metastatic stage at study entry, not eligible for definite surgery or radiation, without EGFR, ALK and ROS1 gene alterations eligible for targeted therapy; other sensitizing mutations known to be immunosensitive are eligible in case of lack of local access to targeted therapy (i.e.; KRAS G12C and BRAF mutations) after Sponsor' agreement 3. Patients who progressed after ≥ 24 weeks of first-line CT-ICI, including ≥12 weeks of anti-PD(L)1 as monotherapy or in combination with another ICI prior to randomization (i.e.; ICI secondary resistance); a radiological tumor assessment by the Investigator at 24 weeks (± 2 weeks) after the start of ICI is needed to exclude PD; induction treatment with first-line CT-ICI should contain at least 2 cycles of platinum-based CT except if contraindication to platinum

1. Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas) 2. Patients with known hypersensitivity to the active substances or to any of the excipients of OSE2101 or docetaxel 3. Patients with PD during induction first-line CT-ICI (to exclude hyper progression and fast progression to CT-ICI) or with PD within 24 weeks of ICI; chemotherapy, other cytotoxic agent or antiangiogenics in combination with ICI within 12 weeks prior to randomization are not authorized; patients who stopped ICI due to toxicity or other reason than PD are not eligible