Evaluation of UCPVax Plus Nivolumab as Second Line Therapy in Advanced Non Small Cell Lung Cancer

Inclusion Criteria:

* Signed informed consent
* Age ≥ 18 years
* Histologically or cytologically confirmed advanced NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other)
* Advanced NSCLC cancer patient with progressive disease after a first line of combo chemotherapy plus anti-PD-1 or chemotherapy plus anti-PD-L1 combination
* Measurable disease defined according to iRECIST v1.1 guidelines
* Patients must have a mandatory treatment-free interval of at least 21 days following previous systemic anti-cancer treatments
* Patients who have received previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 with the exception of Grade 2 alopecia
* Performance status 0 or 1 on the ECOG scale
* Females must be using highly effective contraceptive measures and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential. Females of childbearing potential should use reliable methods of contraception from the time of the screening until 5 months after discontinuing study treatment. Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 7 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 7 months after discontinuing study treatment.
* Registration in a national health care system.
* Ability to comply with the study protocol, in the Investigator's judgment

Exclusion Criteria:

* Diagnosis of additional malignancy within 2 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer
* Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
* Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
* Patient under guardianship, curatorship or under the protection of justice
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
* Known active central nervous system metastases and/or carcinomatous meningitis
* Uncontrolled brain metastases
* Presence of EGFR mutation, ALK or ROS1 translocation
* history of hyperprogression during first line treatment with chemotherapy plus immunotherapy
* Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition
* Active or chronic hepatitis B or C and/or HIV positive or known history of active Covid-19 infection, or a known history of active Tuberculosis bacillus
* Any immunosuppressive therapy (i.e. corticosteroids \>10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy
* Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed
* Active or history of autoimmune disease or immune deficiency
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of Nivolumab formulation
* History of idiopathic or secondary pulmonary fibrosis or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy
* Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Treatment with therapeutic oral or IV antibiotics within 4 weeks prior to initiation of study treatment
* Receipt of a live, attenuated vaccine within 4 weeks prior to the initiation of treatment or anticipation that such a live, attenuated vaccine will be required during the study
* Patients requiring oxygen therapy
* For patients with a known cardiac history or with cardiac events occurring after first-line chemoimmunotherapy: LEVF\<40% ; troponin \> ULN; BNP \> ULN
* Inadequate hematology, hepatic, renal functions or others inadequate laboratory values