Personalised Neoantigen-targeting Cancer Vaccine NECVAX-NEO1 in Anti-PD-1/PD-L1 Therapy 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 at least 18 years old at the time of ICF signature.

5. Patients with solid tumors with measurable disease according to RECIST 1.1, plannedto be treated with a PD-1 or PDL1 inhibitor as first- or second-line standard ofcare therapy according to national/institutional guidelines:

6. Patients with tumor or metastasis accessible for guided needle biopsy or resection.

7. Patients with adequate bone marrow function at Screening, confirmed at Baseline,including:

8. absolute neutrophil count (ANC) ≥1.5 × 109/L; patients with documented benigncyclical neutropenia are eligible if white blood cell count is ≥1.5 × 109/L,with ANC ≥1.0 × 109/L, leukocytes ≥4.0 × 109/L, and lymphocytes ≥0.6 × 109/L;

9. platelets ≥ 100 × 109/L;

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

11. International Normalized Ratio (INR) <1.5 × the upper limit of normal (ULN);patients treated with vitamin K antagonist are eligible if INR <3 (at Screening andconfirmed at Baseline).

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

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

14. aspartate aminotransferase (AST) level ≤2.5 × ULN, and alanine aminotransferase (ALT) level ≤2.5 × ULN, or, for patients with documented metastatic disease tothe liver, AST and ALT levels ≤5 × ULN.

15. Patients with adequate renal function at Screening, confirmed at Baseline, definedby estimated glomerular filtration rate (eGFR) ≥ 30 mL/min using 2021 CKD-EPIcreatinine equation (eGFR =142min(standardized Scr/K, 1)αmax(standardized Scr/K, 1)-1.200 *0.9938Age *1.012 [if female] where K = 0.7 [females] or 0.9 [males], α = -0.241 [females] or -0.302 [males], min = indicates the minimum of Scr/K or 1, andmax = indicates the maximum of Scr/K or 1).

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

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

18. Life expectancy of at least 6 months at the time of ICF signature, according to theInvestigator's judgement at the time of ICF signature.

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. Symptomatic brain metastasis.

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

4. Previous malignant disease (other than the tumor disease for this trial) within thelast 5 years (except adequately treated non-melanoma skin cancers and carcinoma insitu of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a completeremission without further recurrence was achieved at least 2 years prior toScreening, and the patient is deemed to have been cured with no additional therapyrequired or anticipated to be required.

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

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

7. patients with vitiligo, psoriasis, alopecia not requiring immunosuppressivetreatment, are eligible.

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

9. History of uncontrolled intercurrent illness, including but not limited touncontrolled hypertension (high blood pressure despite of combination therapy withdiuretic/CCB/ACE or ARB).

10. 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).

11. 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.

12. Other severe acute or chronic medical conditions (if there is one of the medicalconditions at baseline, the patient should not be treated), including

13. immune colitis

14. inflammatory bowel disease

15. history of severe vomiting or diarrhea not having resolved to Grade 1 atBaseline

16. immune pneumonitis

17. pulmonary fibrosis

18. psychiatric conditions including recent (within the last year) or activesuicidal ideation or behavior

19. laboratory abnormalities that may increase the risk associated with trialparticipation or trial treatment administration or may interfere with theinterpretation of trial results and, in the judgement of the Investigator,would make the patient inappropriate for entry into this trial.

20. History of small intestine resection surgery or other major gastrointestinal surgery

21. Active infection requiring systemic therapy with antibiotics (at both Screening andBaseline).

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

23. Patients with increased anesthesiological risk (e.g. known or predicted difficultairway) if general anesthetic is required.

24. Patients with increased bleeding risk (e.g. coagulopathies) and patients onanticoagulants.

25. 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).

26. Women who are pregnant or breastfeeding, or women of childbearing potential (definedas any woman who is not surgically sterile with a hysterectomy and/or bilateraloophorectomy or ≥ 12 moths of amenorrhea and at least 50 years of age) not willingto use highly effective methods of birth control up to 6 months after the last doseof IMP. Males of child-bearing potential not willing to use a highly effectivemethod of birth control to avoid pregnancy with any partner during the study anduntil 90 days after the last dose of IMP

27. Known history of drug/substance abuse. Prior and concomitant medication

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

29. Treatment in any other clinical trial medication within 30 days, before Screening.

30. Any other condition or treatment that, in the opinion of the Investigator, mightinterfere with the trial.

31. Current drug or substance abuse.

32. Chronic concurrent therapy within 2 weeks before the trial treatment or expectedduring the trial treatment period with:

33. corticosteroids (except systemic corticosteroids up to 10 mg prednisolone orequivalent daily dose [oral, intramuscular, or intravenous]).

34. immunosuppressive agents.

35. antibiotics.

36. any other anticancer therapy or concurrent anticancer treatment (except forother checkpoint inhibitors in combination with the anti-PD-1 or anti-PD-L1monoclonal antibody), for example, cytoreductive therapy, radiotherapy with theexception of palliative short course, limited field (i.e., ≤10 fractions and ≤30% bone marrow involvement or per institutional standard) radiotherapy, whichmay be administered during the trial. However, IMP dosing must be suspended atleast 14 days prior to the start of radiotherapy and must not be resumed untilat least 14 days after the last radiotherapy fraction, cytokine therapy, exceptfor erythropoietin. Other

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

38. 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).

39. Legal incapacity or limited legal capacity.

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