Safety and Tolerability of CVHNLC Plus Pembrolizumab in Patients With Squamous Non Small-Cell Lung Cancer (sqNSCLC)

Exclusion Criteria

• •1. Disease progression on or within 12 months after the last dose of (neo-)adjuvant anti PD-(L)1 treatment before start of first-line treatment.
• •2. Prior radiotherapy within 2 weeks before start of trial treatment.
• •3. History of other malignancies unless the patient has undergone potentially curative treatment without evidence of recurrence within the last 3 years. Exception is BCC or carcinoma in situ of any site that has been adequately treated (with the exception of systemic therapy).
• •4. Previous anaphylactic or severe allergic reaction to LNP-formulated drug or (mRNA) vaccine (or known allergy to any other component of CVHNLC).
• •5. Allergy to aminoglycoside or beta-lactam antibiotics.
• •6. History of previous permanent discontinuation of anti-PD-(L)1 therapy due to toxicity or any other contraindications to treatment with pembrolizumab, including severe hypersensitivity to anti-PD-1 checkpoint inhibitors, its active substance, or one of its excipients.
• •7. Abnormal (≥ Grade 2 NCI-CTCAE v5.0) laboratory values as follows:
• •1. Hemoglobin \< 10 g/dL (6.2 mmol/L).
• •2. White blood cell (WBC) count decrease \< 2.5 ×109/L.
• •3. Absolute neutrophil count (ANC) decrease \< 1.5 ×109/L.
• •4. Absolute lymphocyte count (ALC) decrease \< 0.5 ×109/L.
• •5. Platelet count decrease \< 75 ×109/L.
• •6. Bilirubin \> 1.5 × upper limit of normal (ULN according to the performing lab's reference range), except for patients with Gilbert's syndrome.
• •7. Alanine aminotransferase (ALT) \> 3 × ULN (or ≤ 5 in patients with liver metastasis).
• •8. Aspartate aminotransferase (AST) \> 3 × ULN. (or ≤ 5 in patients with liver metastasis).
• •9. Serum creatinine increased \> 1.5 × ULN or creatinine clearance \< 50 mL/min.
• •10. Serum Albumin \< 30 g/L.
• •8. Received steroid treatment with doses exceeding 10 mg prednisolone or equivalent per day within 3 days prior to enrollment and/or requiring continued treatment with steroid doses above 10 mg/day prednisolone or equivalent or any other systemic immunosuppressive treatment within 28 days prior to enrollment or requiring chronic immunosuppression with such treatment. Inhalation steroids or topical steroids are allowed.
• •9. Active infections requiring antibiotic treatment, associated with fever \> 38°C or expected to potentially result in severe disease.
• •10. Patients with known active hepatitis B (presence of HBsAg) or hepatitis C (presence of Hep C Ab) at screening or within 3 months prior to first trial treatment. In case of positive Hep C Ab, subjects may be enrolled in case of a negative confirmatory hepatitis C virus (HCV) RNA polymerase chain reaction (PCR) test.
• •11. Patients with seropositivity of human immunodeficiency virus (HIV).
• •12. Active autoimmune diseases (except for vitiligo or autoimmune thyroid disease that is stable under treatment), requiring treatment with steroids, disease modifying agents or immunosuppressants.
• •13. Brain metastases or evidence of leptomeningeal tumor spread (with exception of stable brain metastases controlled by radiotherapy or other treatment without need for steroid treatment).
• •14. Immunosuppression other than related to prior treatment of malignancy (i.e., platinum-based chemotherapy).
• •15. Previous hematopoietic stem cell or solid organ transplantation.
• •16. Any condition that in the judgment of the Investigator is likely to prevent compliance with trial procedures.
• •17. Previous immune-mediated pneumonitis, myocarditis, immune-mediated hepatitis, encephalitis or Guillain-Barré syndrome of any grade, any occurrence of a ≥ Grade 3 immune-mediated AE during previous treatment with pembrolizumab (with the exception of endocrinopathies stable under hormone replacement).
• •18. Patients with impaired coagulation or any bleeding disorder in whom an intramuscular injection or blood draw is contraindicated.
• •19. History of myocarditis or pericarditis within the last 6 months or history of myocarditis or pericarditis following mRNA COVID-19 vaccination.
• •20. Previous prophylactic mRNA vaccination (e.g., SARS-CoV2) or live attenuated vaccination within 30 days prior to first administration of CVHNLC treatment and other vaccines within 2 weeks prior to first administration of CVHNLC treatment.
• •21. Previous anticancer vaccine administrations.
• •22. Serious illness or condition, which according to the Investigator poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following:
• •1. Clinically significant cardiovascular disease (myocardial infarction or stroke within the last 6 months, uncontrolled angina within last 3 months, diagnosed or suspected clinically significant ventricular arrhythmias, ejection fraction \< 45%, cerebrovascular event within last 6 months, uncontrolled hypertension \[blood pressure \> 160 mmHg systolic and 100 mmHg diastolic despite\] medication).
• •2. New York Heart Association (NYHA) Class III to IV congestive heart failure.
• •3. Symptomatic peripheral vascular disease.
• •4. Severe pulmonary disease (e.g., severe chronic obstructive pulmonary disease or pulmonary fibrosis), active or history of non-infectious pneumonitis or interstitial lung disease requiring steroids.
• •23. Uncontrolled diabetes (repeated episodes of severe hypo- or hyperglycemia requiring hospitalization).
• •24. Severe mental retardation/impairment, psychiatric conditions or substance abuse resulting in inability to understand informed consent or affecting patient's cooperation in the trial.
• •25. Pregnant or breastfeeding patients.
• •26. Concurrent or prior (within 30 days or at least 5 half-lives of investigational product, whatever is longer prior to trial enrollment) participation in another investigational clinical trial studying an investigational product or treatment regimen.
• •27. Patients with any contraindications to the SOC/AxMP as detailed in the approved product label or SmPC/USPI.