GUCY2C Prime-Boost Vaccination for Advanced Colorectal and Small Bowel Adenocarcinomas (NCT07417488) | Clinical Trial Compass
RecruitingPhase 1
GUCY2C Prime-Boost Vaccination for Advanced Colorectal and Small Bowel Adenocarcinomas
United States18 participantsStarted 2026-04-21
Plain-language 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.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. 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.
What they're measuring
1
Rate of Dose Limiting Toxicities (DLT) to determine recommended Phase 2 dose (RPTD) of Lm-GUCY2C vaccine boosts following Ad5.F35-hGUCY2C-PADRE vaccine
Timeframe: 28 days after first Lm-GUCY2C vaccination
2
Number of patients with dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
Timeframe: 28 days after first Lm-GUCY2C vaccination
✓. Adequate venous access by peripheral vein evaluation
Exclusion criteria
✕. 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:
✕. 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)