Colorectal CancerPhase 1NCT07417488
GUCY2C Prime-Boost Vaccination for Advanced Colorectal and Small Bowel Adenocarcinomas
A Phase 1 study testing Ad5.F35-hGUCY2C-PADRE vaccine, Lm-GUCY2C vaccine and CT Scan in people with Colorectal Cancer and Small Bowel Adenocarcinoma, run by Thomas Jefferson University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Small Bowel Adenocarcinoma
- What is being tested?
- Ad5.F35-hGUCY2C-PADRE vaccine, Lm-GUCY2C vaccine and CT Scan
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2026to Apr 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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.
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- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Daniel Lin, MD, 215-600-9151, ONCTrialNow@jefferson.edu
About this study
Official title: 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
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.
Read the 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
- Being tested
- Ad5.F35-hGUCY2C-PADRE vaccine, Lm-GUCY2C vaccine, CT Scan
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad5.F35-hGUCY2C-PADRE vaccineBiological
Also called Ad5/F35-hGCC-PADRE, Adenovirus 5/F35-HGCC-PADRE
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.
Lm-GUCY2C vaccineBiological
Also called Listeria monocytogenes - GUCY2C, Listeria monocytogenes - GCC
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.
CT ScanDiagnostic test
Also called Computed Tomography 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Ad5.F35-hGUCY2C-PADRE vaccine; Biological: Lm-GUCY2C vaccine; Diagnostic Test: CT Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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)
Number of participants experiencing treatment-emergent adverse events following administration of study vaccines.
Measured: Up to 1 year after first vaccination
T-cell Responses to GUCY2C measured by enzyme-linked immunosorbent spot (ELISpot) assay
Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a small GUCY2C-specific T-cell response can be expected after Ad5.F35-hGUCY2C-PADRE, but a significant T-cell response is expected at Days 29 and 57 (four weeks after each Lm-GUCY2C dose). Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method. A subject with a response at either Day 29 or Day 57 will be considered a responder. Supporting analysis will model the trajectory of GUCY2C-specific T-cell responses over time using mixed effects linear regression.
Measured: 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
(pan-Ig) ELISA will be used to detect responses, which will be graded on a scale of mean absorbance at 405 nm. Some GUCY2C-specific humoral response may be detectable at Day 29, but a stronger response is expected at measurement on Day 57. Subjects that fail to produce an end-point titer (no dilution is greater than pre-treatment) by Day 57 will be considered non-responders. Otherwise, responses will be measured on a continuous basis and compared both within and among cohorts at the end of the study. Supporting analysis will model the trajectory of GUCY2C-specific pan-Ig responses over time using mixed effects linear regression.
Measured: 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 measurement of circulating tumor DNA (ctDNA) will occur prior to beginning therapy with any administration of a vaccine. This will be used as a baseline for comparison at other time points throughout the study (increasing or decreasing if positive or negative). ctDNA will be measured at Days 29 and 57, and measurements will be categorized into one of five possible results at each time points: 1) decrease from baseline, 2) increase from baseline, 3) conversion from positive to negative, 2) conversion from negative to positive, and 5) maintenance of negative result. The time of conversion will be notated, where applicable.
Measured: 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)
The duration of overall response is measured from the time the criteria are first met for a Complete Response (CR) or Partial Response (PR)-whichever occurs first-until the first date that recurrent or Progressive Disease (PD) is objectively documented, using the smallest measurements recorded during the study as the reference for determining PD. The proportion of participants with a best overall response is assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Under RECIST version 1.0, target lesions evaluated by magnetic resonance imaging (MRI) are categorized as follows: a Complete Response (CR) is defined as the disappearance of all target lesions; a Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameters of target lesions; and the Overall Response (OR) represents the combined total of CR and PR.
Measured: Up to 12 months after first vaccination
Disease Control Rate (DCR)
Defined as the time from the first occurrence of the best overall response-Complete Response (CR), Partial Response (PR), or Stable Disease (SD)-to either disease progression or death from any cause during the treatment period.
Measured: At 12 weeks
Characterize the pharmacokinetics (PK) of Ad5.F35-hGUCY2C-PADRE vaccine vector
Vector (Adenovirus Serotype 5/35 [Ad5.F35]-Guanylyl Cyclase C [GUCY2C]-PADRE) and Listeria monocytogenes-GUCY2C (Lm-GUCY2C) DNA will be quantified in blood using quantitative polymerase chain reaction (qPCR) to assess pharmacokinetics in the bloodstream.
Measured: Screening through 4 weeks after final Lm-GUCY2C administration
Characterize the shedding assessment for the Ad5.F35-hGUCY2C-PADRE vaccine vector
Vector (Ad5.F35-GUCY2C-PADRE and Lm-GUCY2C) DNA will be quantified by qPCR in saliva, urine, and feces to determine shedding from the subject.
Measured: Screening through 4 weeks after final Lm-GUCY2C administration
Characterize the pharmacokinetics (PK) of Lm-GUCY2C vaccine vector
Vector (Ad5.F35-GUCY2C-PADRE and Lm-GUCY2C) DNA will be quantified by qPCR in blood to determine pharmacokinetics in blood)
Measured: Screening through 4 weeks after final Lm-GUCY2C administration
Characterize the shedding assessment for the Lm-GUCY2C vaccine vector
Vector (Ad5.F35-GUCY2C-PADRE and Lm-GUCY2C) DNA will be quantified by qPCR in saliva, urine, and feces to determine shedding from the subject.
Measured: Screening through 4 weeks after final Lm-GUCY2C administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start21 Apr 2026
- Primary completionOct 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Daniel Lin, M.D., Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07417488
- Sponsor's protocol ID
- iRISID-2025-1138
- Other IDs
- JT 44551, CA210829
- Status last verified
- Oct 2026
- First submitted
- 10 Feb 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No