GUCY2C Prime-Boost Vaccination for Advanced Colorectal and Small Bowel Adenocarcinomas

Inclusion Criteria

• •1. Males or females aged ≥ 18 years
• •2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •3. Histologically or cytologically diagnosed, locally advanced or metastatic adenocarcinomas of colorectum or small bowel that have progressed after standard of care therapy or for which no standard therapy exists. Patients for whom standard therapies are intolerable or considered clinically inappropriate by the Investigator are eligible. If a patient refused available standard therapy or Investigator determined standard therapy was inappropriate, the reason for refusal or Investigator determination should be documented.
• •4. Patients with MSS CRC or small bowel adenocarcinoma must have received at least 1) a fluoropyrimidine, 2) oxaliplatin or irinotecan, and 3) a VEGF/VEGF receptor inhibitor unless deemed clinically inappropriate, refused by the patient, or not considered standard practice per institutional standards.
• •5. Patients with MSI-H and/or dMMR CRC or small bowel adenocarcinoma must have received a programmed death-1 or programmed death-ligand 1 (PD-L1) inhibitor unless deemed clinically inappropriate, refused by the patient, or not considered standard practice.
• •6. Have an anticipated life expectancy of greater than 12 weeks
• •7. Have at least 1 extracranial measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Exceptions may be made to this inclusion if a patient has biochemical evidence (ctDNA) of disease upon discussion with principal investigator provided other eligilbity criteria are fulfilled.
• •8. Adequate venous access by peripheral vein evaluation
• •9. Have adequate hematologic function at screening, as evidenced by:
• •1. ANC ≥ 1500 cells/mL; no growth factor support within 14 days prior to Screening assessment
• •2. Platelets ≥ 75,000 /mL; no transfusion within 14 days prior to Screening assessment
• •3. Hemoglobin ≥ 9.0 g/dL; no transfusion or erythyropoietin support within 14 days prior to Screening assessment.
• •10. Patients must have adequate hepatic function, as evidenced by:
• •1. Albumin ≥ 3.0 mg/dL; no albumin support within 14 days prior to Screening assessment,
• •2. Total bilirubin ≤ 2.0 x upper limit of normal (ULN), except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤ 1.5 x ULN is required)
• •3. Aspartate aminotransferase (AST) AND alanine aminotransferase ≤ 2.5 x ULN or ≤ 5 x ULN in the presence of liver metastases.
• •4. Serum creatinine \< 2.0 mg/dL
• •5. For other blood and urine tests including blood chemistry, hepatic and renal functions, test results should not be worse than grade 1 levels of abnormalities defined by CTCAE, NCI version 5 (CTCAEv5) issued by the US Department of Health and Human Services.
• •11. For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormonal implants) or abstinence must be used throughout the study period and for 28 days after their final vaccine administration. (A barrier method of contraception must be employed by all subjects \[male and female\], regardless of other methods unless abstinent.) A negative serum or urine pregnancy test is required as part of screening. Subjects capable of becoming pregnant include any female who has experienced menarche and has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who are not postmenopausal. Also, subjects assigned female sex at birth who are physiologically still able to become pregnant by similar definitions detailed here. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/ml.
• •12. Be willing to comply with all the study procedures. All subjects must be able to comprehend and sign a written informed consent document