NCT07417488

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This phase 1 study is an open-label study of heterologous prime-boost 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 adenocarcinomas who have progressed on available standard therapies.. Subjects will receive Ad5.F35-hGUCY2C-PADRE intramuscularly (IM) followed by two administrations of the Lm-GUCY2C vaccine intravenously (IV) as described and will be followed primarily to evaluate safety endpoints for the duration of the study (through eight weeks after the first administration of Lm-GUCY2C). The main objective of this Phase I trial is to determine the MTD and the RPTD of this prime-boost vaccination regimen. Subjects will be enrolled by Bayesian optimal interval (BOIN) design in dose-escalation cohorts of three. The first cohort will receive Lm-GUCY2C at a dose of 3 x 10⁸ CFU, and this dose will be escalated to subsequent levels (1 x 10⁹, 3 x 10⁹ CFU) with each cohort according to the BOIN model until the maximum dose, barring excessive rates of dose-limiting toxicities. One dose level will be reserved for de-escalation if necessary (1 x 10⁸ CFU). Subjects will receive treatment over a 12-week period including the Ad5.F35-hGUCY2C-PADRE vaccine, with evaluation of DLTs over 4 weeks following the first Lm-GUCY2C vaccine and clinical and laboratory monitoring after the second Lm-GUCY2C vaccine. Only the necessary safety evaluations will be conducted after Ad5.F35-hGUCY2C-PADRE vaccination. Subjects will be actively followed (clinical and laboratory evaluations) for 12 weeks following first vaccination with Ad5.F35-hGUCY2C-PADRE. Then, they will be followed every 3 months for Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. evaluation until all subjects have had disease progression or have started new anti-cancer therapies or death.

Conditions

• Colorectal Cancer
• Small Bowel Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Ad5.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.
BIOLOGICAL	Lm-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_TEST	CT 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.

Timeline

• Start date: 2026-02-01
• Primary completion: 2027-01-01
• Completion: 2027-01-01
• First posted: 2026-02-18
• Last updated: 2026-02-27

Regulatory

• FDA-regulated drug study