x The NCI Pharmacy Manual contains details regarding sterility release of NCI-4650. Abbreviated Title: mRNA-Based, Cancer Vaccine Version Date: January 23, 2019 28 BASELINE EVALUATIONS 3.4.1 Within 7 Days Prior to the First Vaccination (Day 0) x Physical examination, including ECOG (see Appendix B ) x Weight and vital signs x Baseline blood tests: o CBC w/differential o Acute Care Panel (sodium, potassium, chlo ride, bicarbonate, creatinine, glucose, BUN), Hepatic Panel (alkaline phosphatase, AST, ALT, total bilirubin, direct bilirubin), Mineral Panel (a lbumin, calcium, magnesium, phosphorus), Uric acid, Creatinine kinase, Lactate dehydrogenase, Total protein o PT-INR/PTT o Anti-CMV antibody titer, HSV and VZV serology, and EBV panel (Note: Patients who are known to be positive do not need to be retested. May be performed within 3 months prior to Part Two registration.) x ȕ-HCG pregnancy test (serum or urine) on all women of child-bearing potential x Urinalysis, with culture if indicated x Chest x-ray x EKG x Repeat imaging if not performed within 4 weeks of Day 0. This may include CT, MRI, PET, and/or photography. 3.4.2 Within 2 Days Prior to the First Vaccination (Day 0) x Lymphocyte phenotyping (TBNK) x Review of baseline symptoms x Research samples, as described in Section 5.3 ON-STUDY EVALUATIONS 3.5.1 Within 2 Days Prior to Each Subsequent Vaccination (Days 14, 28, & 42 (± 5 days)) x Physical examination, including ECOG (see Appendix B ) x Weight and vital signs x Toxicity assessment, including a review of systems x CBC w/differential x Acute Care Panel (sodium, potassium, chlori de, bicarbonate, creatinine, glucose, BUN), Hepatic Panel (alkaline phosphatase, AST, ALT, total bilirubin, direct bilirubin), Mineral Panel (albumin, calcium, magnesium, phosphorus ), Uric acid, Creatinine kinase, Lactate dehydrogenase, Total protein Abbreviated Title: mRNA-Based, Cancer Vaccine Version Date: January 23, 2019 29x ȕ-HCG pregnancy test (serum or urine) on all women of child-bearing potential x Research samples, as described in Section 5.3 3.5.2 After Each Vaccination x Vital signs will be mon itored hourly (± 15 minutes) for two hours. The post- administration monitoring period may be adjusted by the PI. POST-TREATMENT (FOLLOW -UP) EVALUATIONS 3.6.1 First Follow-up Evaluation All patients (unless the patient receives a second course of treatment) will return to the NIH Clinical Center for their first follow-up evaluati on on day 56 (± 5 days), which is approximately two weeks after the fourth vaccination. If a patient receives a second course of four vaccines, the first follow-up evaluation will be two weeks (± 5 days) after the eighth vaccination. At the first follow-up evaluation, patients will undergo: x Physical examination, including ECOG (see Appendix B ) x Weight and vital signs x Toxicity assessment, including a review of systems x CBC w/differential x Acute Care Panel (sodium, potassium, chlori de, bicarbonate, creatinine, glucose, BUN), Hepatic Panel (alkaline phosphatase, AST, ALT, total bilirubin, direct bilirubin), Mineral Panel (albumin, calcium, magnesium, phosphorus ), Uric acid, Creatinine kinase, Lactate dehydrogenase, Total protein x Lymphocyte phenotyping (TBNK) x ȕ-HCG pregnancy test (serum or urine) on all women of child-bearing potential x Research samples, as described in Section 5.3. Approximately 72 mL of blood will be obtained. PBMC will be cryopreserved so th at immunologic testing may be performed. This will be performed on protocol 03-C-0277. x Imaging studies as performed at baseline to determine tumor response. If clinically indicated, other scans or x-rays may be performed, e.g.