A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma

Prior treatment

• Concurrent use of systemic steroids or immunosuppressive drugs (use of topical or inhaled steroids will be allowed, see Section 5.7)
• Have received a diagnosis of HIV, hepatitis B, or hepatitis C (subjects who are hepatitis C positive may be enrolled if they are confirmed with negative viral load at screening)
• Have an unhealed surgical wound
• Have had major surgery or significant traumatic injury occurring within 28 days before treatment or anticipated surgery or procedure requiring general anesthesia during the study participation (including four weeks after last dose of vaccine).
• Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy

Other illness

• Have a known history or evidence of residual disease after definitive surgery
• Have a history of splenectomy
• Have a history of distal pancreatectomy
• Have any immunodeficiency disease or immunocompromised state (e.g., use of immunosuppressive agents, chemotherapy or radiation therapy within four weeks of study treatment)
• Have active autoimmune disease or history of autoimmune disease or a transplant recipient requiring systemic steroids or other immunosuppressive treatment
• Other malignancy within last 5 years except curatively treated non-melanomatous skin cancer and curatively treated carcinoma in situ of the uterine cervix, or early-stage (stage A or B1) prostate cancer
• Have a history of inflammatory bowel disease
• Have a history of serious reaction to adenovirus
• Have an intercurrent illness that is either life-threatening or of clinical importance such that it might limit study compliance (such illnesses include, but are not limited to, ongoing or active infection, metabolic or neurologic disease, peripheral vascular disease, or psychiatric illness)
• Has a history of use of illicit drugs (e.g., opioids, cocaine, amphetamines, hallucinogens, etc.) that could potentially interfere with adherence to study procedures or requirements

Other

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Have a known metastasis in the brain or central nervous system
• Have insufficient peripheral venous access to permit completion of the study phlebotomy regimen
• Consumes greater than three glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day and cannot refrain from alcohol for the duration of the trial
• Be a woman who is pregnant or breastfeeding
• Patients are currently enrolled in an ongoing clinical trial or trial that could interfere with the protocol-specified requirements

• Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:
• Males or females aged ≥ 18 years 2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. Subjects with tumors specified below, who are at high risk of relapse, have been treated with curative intent, and have no evidence of disease (NED) following front-line therapy with surgery, radiation therapy, and/or chemotherapy. NED includes, where applicable, surgical (macroscopic tumor margin, at the time of surgery), and radiological evidence of disease. Residual lesions identified by microscopic/frozen margins and biochemical markers are permitted. Therapy must have been completed no fewer than four weeks, and no later than 25 weeks, before the first dose of Ad5.F35-hGCC-PADRE. For expansion cohort (2B), colon cancer patients may be enrolled four weeks after completion of standard adjuvant therapies, however there is no upper limit to enrollment as long as patients fulfil other eligibility requirements are ctDNA+.
• For tumor-specific criteria, please refer to the information below:
• Pancreatic ductal adenocarcinoma i. Stage I, II, III
• Neuroendocrine tumors of the pancreas are not permitted b. Colorectal adenocarcinoma i. Stage III; Stage IV following metastasectomy ii. High risk stage II colon cancer defined as (any of):
  • T4
  • Grade ≥ 3
  • Clinical presentation with bowel obstruction or perforation
  • Histological signs of vascular, lymphatic or perineural invasion
  • < 12 lymph nodes examined c. Gastric adenocarcinoma i. Stage IIA, IIB, III
• Gastrointestinal stromal tumors of the stomach are not permitted d. Esophageal adenocarcinoma i. Stage IIB, III
• Esophageal squamous cell carcinomas are not permitted e. Small bowel adenocarcinomas i. Stage III ii. High risk stage II defined as (any of):
• T4
• Grade ≥ 3
• Clinical presentation with perforation or bowel obstruction
• Histological signs of vascular, lymphatic or perineural invasion
• <5 lymph nodes for duodenal or <8 lymph nodes for jejunal/ ileal tumor location 5. Have an anticipated life expectancy of greater than 12 weeks 6. Have adequate organ function at screening
  • ANC ≥ 1000 cells/mL
  • Platelets ≥ 75,000 /mL
  • Hemoglobin ≥ 9.0 g/dL
  • Serum creatinine < 2.0 mg/dL
  • 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 issued by the US Department of Health and Human Services.
  • 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.
  • Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. 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.
  • Be willing to comply with all the study procedures. 9. All subjects must be able to comprehend and sign a written informed consent document 10. For expansion cohort (2B) only, colon cancer patients must be ctDNA positive using CLIA-certified commercially available assays obtained as part of standard of care.