NECVAX-NEO1 in Addition to Checkpoint Inhibitor in Patients With Solid Tumors

Inclusion Criteria:

1. Patients able to understand and follow instructions during the trial.

2. Patients able and willing to give written informed consent, signed and dated.

3. Male or female patients.

4. Patients aged 18 to 75 years old inclusive at the time of ICF signature.

5. Cancer patients with measurable disease according to RECIST 1.1, treated for atleast three (3) months with an anti-PD-1 or anti-PDL1 checkpoint inhibitor as first-or second-line monotherapy, according to the Summary of Product Characteristics (SmPC) and national/institutional guidelines, for one of the following tumor types:

6. non-small cell lung cancer, or

7. cutaneous melanoma, or

8. urothelial carcinoma, or

9. renal cell carcinoma, or

10. squamous cell cancer of head and neck.

11. Patients with SD or PR according to RECIST 1.1 at Screening

12. Patients with tumor or metastasis accessible for guided needle biopsy or resectabletumor in case of cutaneous melanoma when needle biopsy is not performed.

13. Patients with adequate bone marrow function, including:

14. ANC ≥ 1.5 × 109/L; patients with documented benign cyclical neutropenia areallowed if white blood cell count is ≥ 1.5 × 10E9/L, with ANC ≥ 1.0 × 10E9/L,leukocytes ≥ 4.0 × 10E9/L, and lymphocytes ≥ 0.6 × 10E9/L;

15. platelets ≥ 100 × 10E9/L;

16. hemoglobin ≥ 9 g/dL (may have been transfused);

17. International Normalized Ratio (INR) < 1.5 × Upper Limit of Normal (ULN); patientstreated with vitamin K antagonist are eligible if INR < 3.

18. Patients with adequate hepatic function at Screening, confirmed at Baseline, definedby

19. total bilirubin level ≤ 1.5 × ULN; patients with documented Gilbert disease areallowed if total bilirubin ≤ 3 × ULN;

20. aspartate aminotransferase (AST) level ≤ 2.5 × ULN, and alanineaminotransferase (ALT) level ≤ 2.5 × ULN, or, for patients with documentedmetastatic disease to the liver, AST and ALT levels ≤ 5 × ULN.

21. Patients with adequate renal function at Screening, confirmed at Baseline, definedby an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gaultformula.

22. Patients must be able to undergo MRI or CT scan for tumor follow-up.

23. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

24. Life expectancy of at least six (6) months according to the Investigator'sjudgement.

Exclusion Criteria:

Medical and surgical history, and diseases

1. History of any disease, metabolic dysfunction, physical examination finding, orclinical laboratory finding that, based on the Investigator's judgement, provides areasonable suspicion of a disease or condition that contraindicates the use of theIMP or that might affect the interpretation of the trial results or render thepatient at high risk for treatment complications.

2. Brain metastasis.

3. Previously reported immune-related checkpoint inhibitor side effects of CTCAE Grade 3 or higher not having resolved to Grade 1 within six (6) weeks before inclusion.

4. Any significant co-morbidity which, according to the Investigator's judgement, makespatient compliance to trial conditions unlikely.

5. Previous malignant disease (other than the tumor disease for this trial) within thelast five (5) years (except adequately treated non-melanoma skin cancers andcarcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate)unless a complete remission without further recurrence was achieved at least two (2)years prior to Screening, and the patient is deemed to have been cured with noadditional therapy required or anticipated to be required.

6. Prior organ transplantation, including allogeneic stem cell transplantation.

7. Congenital or any other immunodeficiency syndromes, or any active autoimmune diseasethat might deteriorate when receiving an immunostimulatory agent, except for:

8. patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroiddisease not requiring immunosuppressive treatment, who are eligible.

9. administration of steroids through a route known to result in a minimalsystemic exposure (topical, intranasal, intro-ocular, or inhalation), which isacceptable.

10. History of uncontrolled intercurrent illness, including but not limited touncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%);

11. Known prior hypersensitivity to the IMP or any component in its formulations or anyother drug scheduled or likely to be given during the trial, including known severehypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).

12. Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade > 1); however,alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 AEs not constituting asafety risk based on Investigator's judgement are acceptable.

13. Other severe acute or chronic medical conditions, including immune colitis,inflammatory bowel disease, history of severe vomiting or diarrhea not havingresolved to Grade 1 at Baseline, immune pneumonitis, pulmonary fibrosis, orpsychiatric conditions including recent (within the last year) or active suicidalideation or behavior, or laboratory abnormalities that may increase the riskassociated with trial participation or trial treatment administration or mayinterfere with the interpretation of trial results and, in the judgement of theInvestigator, would make the patient inappropriate for entry into this trial.

14. History of small intestine resection surgery or other major gastrointestinalsurgery.

15. Active infection requiring systemic therapy.

16. Known history of human immunodeficiency virus (HIV) or known acquiredimmunodeficiency syndrome or multi-drug resistant gram-negative bacteria.

17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at Screening (positiveHBV surface antigen or HCV RNA if anti-HCV antibody Screening test positive).

18. Women of childbearing potential. Prior and concomitant medication

19. Live vaccines within 30 days prior to trial treatment.

20. Treatment in any other clinical trial within 30 days or within five (5) half-livesof any prior treatment, before Screening;

21. Any other condition or treatment that, in the opinion of the Investigator, mightinterfere with the trial, or current drug or substance abuse;

22. Chronic concurrent therapy within two (2) weeks before the trial treatment orexpected therapy during the trial treatment period with:

23. corticosteroids (except steroids up to equivalent of dexamethasone 4 mg dailydose).

24. immunosuppressive agents.

25. antibiotics.

26. any other anticancer therapy or concurrent anticancer treatment, for example,cytoreductive therapy, radiotherapy [with the exception of palliative shortcourse, limited field (ie, ≤ 10 fractions and ≤ 30% bone marrow involvement orper institutional standard) radiotherapy, which may be administered during thetrial. However, IMP dosing must be suspended at least 14 days prior to thestart of radiotherapy and must not be resumed until at least 14 days after thelast radiotherapy fraction], immune therapy, or cytokine therapy, except forerythropoietin. Other

27. Inability to understand the Protocol requirements, instructions and trial-relatedrestrictions, the nature, scope, and possible consequences of the trial.

28. Unlikely to comply with the Protocol requirements, instructions and trial-relatedrestrictions; e.g., uncooperative attitude, inability to return for follow-upvisits, and improbability of completing the trial.

29. Legal incapacity or limited legal capacity.

30. Any condition which results in an undue risk for the patient during the trialparticipation according to the Investigator.