RecruitingPhase 1NCT07417488

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

A Phase I, Single-Center, Dose Escalation Trial of Heterologous Prime-Boost Vaccination With Ad5.F35-hGUCY2C-PADRE and Lm-GUCY2C Vaccines in Adults With Advanced Colorectal and Small Bowel Adenocarcinomas

Sponsor

Thomas Jefferson University

Enrollment

18 participants

Start Date

Apr 21, 2026

Study Type

INTERVENTIONAL

Conditions

Colorectal, Cancer Small-bowel Adenocarcinoma

Summary

This is an open-label, non-randomized, single-center, dose-escalation Phase 1 trial using a heterologous prime-boost strategy of vaccination with Ad5.F35-hGUCY2C-PADRE and recombinant Listeria monocytogenes (Lm-GUCY2C) vaccines in patients with advanced solid tumors including colorectal cancer, and small bowel adenocarcarcinomas who have progressed on available standard therapies. The study treatment will begin with Ad5.F35-hGUCY2C-PADRE vaccine administered intramuscularly (IM) once at the recommended Phase 2 dose (RPTD) dose, followed four weeks later by two administrations of Lm-GUCY2C intravenously (IV) at one of three escalating dose levels, four weeks apart. Treatment-related toxicity and development of immune responses will be evaluated every four weeks through week 8 after initial Lm-GUCY2C vaccination. Primary endpoints will include maximum tolerated dose (MTD) and safety and tolerability as measured by treatment emergent adverse events (TEAEs) and clinically significant changes in safety laboratory tests in the dose limiting toxicity (DLT) evaluation period defined as 4 weeks after the initial Lm-GUCY2C vaccination.

Eligibility

Min Age: 18 Years

Inclusion Criteria20

Males or females aged ≥ 18 years
Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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.
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.
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.
Have an anticipated life expectancy of greater than 12 weeks
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.
Adequate venous access by peripheral vein evaluation
Have adequate hematologic function at screening, as evidenced by:
ANC ≥ 1500 cells/mL; no growth factor support within 14 days prior to Screening assessment
Platelets ≥ 75,000 /mL; no transfusion within 14 days prior to Screening assessment
Hemoglobin ≥ 9.0 g/dL; no transfusion or erythyropoietin support within 14 days prior to Screening assessment.
Patients must have adequate hepatic function, as evidenced by:
Albumin ≥ 3.0 mg/dL; no albumin support within 14 days prior to Screening assessment,
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)
Aspartate aminotransferase (AST) AND alanine aminotransferase ≤ 2.5 x ULN or ≤ 5 x ULN in the presence of liver metastases.
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 (CTCAEv5) 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. 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.
Be willing to comply with all the study procedures. All subjects must be able to comprehend and sign a written informed consent document

Exclusion Criteria24

An individual who meets any of the following criteria will be excluded from participation in this study:
History of splenectomy
History of infection with listeriosis or has prior serious reaction to adenovirus
Infection requiring systemic antibiotics within 1 week prior to administration of study intervention
Concurrent use of systemic steroids or immunosuppressive drugs (including TNF pathway inhibitors) with exceptions including:
Topical, ocular, intra-articular, intranasal, and inhalation corticosteroids (with minimal systemic absorption)
Adrenal replacement steroid dose < 10 mg daily prednisone
A brief (fewer than three days) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction cause by a contrast allergen)
Subjects who have implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g., artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)). Chest wall infus-a-port catheter may be used for treatment administration and will not be subject to this exclusion.
Has any immunodeficiency disease or immunocompromised state (e.g., use of immunosuppressive agents including TNF pathway inhibitors, chemotherapy, PI3 kinase inhibitors or radiation therapy within four weeks of study treatment)
Has active or history of autoimmune disease (including inflammatory bowel disease), or is a transplant recipient requiring immunosuppressive treatment
Has 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)
Other malignancy within last 2 years except curatively treated non-melanomatous skin cancer and curatively treated carcinoma in situ (eg, cervix, bladder, breast), or prostate cancer in remission
Known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are:
Radiologically stable, ie, without evidence of progression for at least 12 weeks by repeat imaging
Clinically stable per investigator assessment
Without requirement of steroid treatment for at least 14 days prior to first dose of study vaccine
Has 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 insufficient peripheral venous access to permit completion of the study phlebotomy regimen or infusion of study vaccine
Concurrent use of illicit drugs (e.g., opioids, cocaine, amphetamines, hallucinogens, etc.) that could potentially interfere with adherence to study procedures or requirements.
Be pregnant or breastfeeding
Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to grade 1 or less or baseline except for the following Grade 2 AEs that are considered chronic or irreversible: alopecia, peripheral neuropathy, endocrinopathies stable on therapy, and thromboembolic events stable on anticoagulation with no recurrence for > 6 months. Other Grade 2 AEs may be permitted upon discussion with the PI if not otherwise specified in the protocol.
Are currently enrolled in an ongoing clinical trial or trial that could interfere with the protocol-specified requirements
There are no restrictions on concurrent or prior use of preventative vaccines for infectious diseases including influenza or COVID-19, however it is required to include at least one week interval between vaccines and study agent administration.

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Interventions

BIOLOGICALAd5.F35-hGUCY2C-PADRE vaccine

Ad5.F35-hGUCY2C-PADRE vaccine administered as a single intramuscular injection at a dose of 5 × 10¹² viral particles as the priming vaccination in a heterologous prime-boost vaccination regimen.

BIOLOGICALLm-GUCY2C vaccine

Lm-GUCY2C vaccine administered as an intravenous infusion at dose levels 1 x 10⁸, 3 x 10⁸, 1 x 10⁹, and 3 x 10⁹ colony-forming units (CFU) as booster vaccinations given twice approximately four weeks apart following Ad5.F35-hGUCY2C-PADRE priming.

DIAGNOSTIC_TESTCT Scan

Spiral CT of thorax, abdomen, and pelvis (and other imaging studies as clinically indicated) for disease assessment at Screening and EOT. If a subject cannot have a CT scan (e.g., allergy to contrast dye), MRI results are acceptable.