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

NCT07417488 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: iRISID-2025-1138JT 44551CA210829
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Colorectal Cancer; Small Bowel Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Rate of Dose Limiting Toxicities (DLT) to determine recommended Phase 2 dose (RPTD) of Lm-GUCY2C vaccine boosts following Ad5.F35-hGUCY2C-PADRE vaccine

  Number of Participants who experience a dose-limiting toxicity

  28 days after first Lm-GUCY2C vaccination

• Number of patients with dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period

  Number of participants who experience at least once dose-limiting toxicity during the maximum tolerated dose (MTD) evaluation period.

  28 days after first Lm-GUCY2C vaccination

Secondary Outcomes (10)

• Number of Treatment Emergent Adverse Events (TEAEs) as defined by the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5)

  Up to 1 year after first vaccination

• T-cell Responses to GUCY2C measured by enzyme-linked immunosorbent spot (ELISpot) assay

  Baseline through Week 12 after first vaccination with optional collections and analyses until end of follow-up (when all subjects reach 24 months of follow-up)

• Humoral Responsess to GUCY2C

  Baseline through Week 12 after first vaccination with optional collections and analyses until end of follow-up (when all subjects reach 24 months of follow-up)

• Change in ctDNA Levels

  Baseline through Week 12 after first vaccination with optional collections and analyses until end of follow-up (when all subjects reach 24 months of follow-up)

• Overall Response Rate (ORR)

  Up to 12 months after first vaccination

Study Arms (4)

Arm 1 Dose Level -1: Lm-GUCY2C 1 x 10⁸

EXPERIMENTAL

Participants receive Ad5.F35-hGUCY2C-PADRE vaccine, administered as a single intramuscular (IM) injection (5 × 10¹² viral particles), followed by Lm-GUCY2C vaccine, administered intravenously at a dose of 1 × 10⁸ colony-forming units (CFU) on two occasions approximately four weeks apart.

Biological: Ad5.F35-hGUCY2C-PADRE vaccine; Biological: Lm-GUCY2C vaccine; Diagnostic Test: CT Scan

Arm 2 Dose Level 1: Lm-GUCY2C 3 x 10⁸

EXPERIMENTAL

Participants receive Ad5.F35-hGUCY2C-PADRE vaccine, administered as a single intramuscular (IM) injection (5 × 10¹² viral particles), followed by Lm-GUCY2C vaccine, administered intravenously at a dose of 3 × 10⁸ colony-forming units (CFU) on two occasions approximately four weeks apart.

Biological: Ad5.F35-hGUCY2C-PADRE vaccine; Biological: Lm-GUCY2C vaccine; Diagnostic Test: CT Scan

Arm 3 Dose Level 2: Lm-GUCY2C 1 x 10⁹

EXPERIMENTAL

Participants receive Ad5.F35-hGUCY2C-PADRE vaccine, administered as a single intramuscular (IM) injection (5 × 10¹² viral particles), followed by Lm-GUCY2C vaccine, administered intravenously at a dose of 1 × 10⁹ colony-forming units (CFU) on two occasions approximately four weeks apart.

Biological: Ad5.F35-hGUCY2C-PADRE vaccine; Biological: Lm-GUCY2C vaccine; Diagnostic Test: CT Scan

Arm 4 Dose Level 3: Lm-GUCY2C 3 x 10⁹

EXPERIMENTAL

Participants receive Ad5.F35-hGUCY2C-PADRE vaccine, administered as a single intramuscular (IM) injection (5 × 10¹² viral particles), followed by Lm-GUCY2C vaccine, administered intravenously at a dose of 3 × 10⁹ colony-forming units (CFU) on two occasions approximately four weeks apart.

Biological: Ad5.F35-hGUCY2C-PADRE vaccine; Biological: Lm-GUCY2C vaccine; Diagnostic Test: CT Scan

Interventions

Ad5.F35-hGUCY2C-PADRE vaccine BIOLOGICAL

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.

Also known as: Ad5/F35-hGCC-PADRE, Adenovirus 5/F35-HGCC-PADRE

Arm 1 Dose Level -1: Lm-GUCY2C 1 x 10⁸; Arm 2 Dose Level 1: Lm-GUCY2C 3 x 10⁸; Arm 3 Dose Level 2: Lm-GUCY2C 1 x 10⁹; Arm 4 Dose Level 3: Lm-GUCY2C 3 x 10⁹

Lm-GUCY2C vaccine BIOLOGICAL

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.

Also known as: Listeria monocytogenes - GUCY2C, Listeria monocytogenes - GCC

Arm 1 Dose Level -1: Lm-GUCY2C 1 x 10⁸; Arm 2 Dose Level 1: Lm-GUCY2C 3 x 10⁸; Arm 3 Dose Level 2: Lm-GUCY2C 1 x 10⁹; Arm 4 Dose Level 3: Lm-GUCY2C 3 x 10⁹

CT Scan DIAGNOSTIC_TEST

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.

Also known as: Computed Tomography Scan

Arm 1 Dose Level -1: Lm-GUCY2C 1 x 10⁸; Arm 2 Dose Level 1: Lm-GUCY2C 3 x 10⁸; Arm 3 Dose Level 2: Lm-GUCY2C 1 x 10⁹; Arm 4 Dose Level 3: Lm-GUCY2C 3 x 10⁹

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead
• United States Department of Defense: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Tomography, X-Ray Computed

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 18, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02