Metastatic Colorectal CancerPhase 1/2NCT06149481
Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC)
A Phase 1/2 study testing Retifanlimab, Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform and N-803 in people with Metastatic Colorectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Each year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Retifanlimab, Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform and N-803
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2024to 31 Oct 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with histologically confirmed colorectal cancer and evidence of metastatic disease.
- Participants must have received, been ineligible to receive, or refused to receive two lines of standard systemic therapy i.e., a fluoropyrimidine with oxaliplatin or irinotecan with bevacizumab, regorafenib, trifluridine, and (if history of RAS wild-type) EGFR-targeted therapy. Participants must have received one line of systemic checkpoint inhibitor if history of advanced microsatellite instability-high [MSI-H/dMMR]) metastatic colon cancer.
- Participants who had progressive disease within 6 months before study treatment following standard adjuvant therapy are eligible if they have not received systemic therapy for metastatic disease. Participants with a history of MSI-H/dMMR must have also received one line of checkpoint inhibitor therapy.
- Age >= 18 years.
- Measurable disease per RECIST 1.1.
- ECOG performance status <= 2.
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- Adequate organ and marrow as a function defined below:
- absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- platelet count >= 100,000 cells/mm^3
- hemoglobin (Hgb) >= 9 g/dL
- total bilirubin level < 1.5 x upper limit of normal (ULN)
- alanine aminotransferase (ALT) <= 2.5 x ULN OR <= 5 x ULN for participants with liver metastases
- aspartate aminotransferase (AST) level <= 2.5 x ULN OR <= 5 x ULN for participants with liver metastases
- creatinine clearance (CrCl) calculated by Cockroft-Gault formula >= 50 mL/min
- Resolution of toxic effect(s) of prior anti-cancer therapy (except alopecia and neuropathy) to Grade <=1 or to <=2 if effective medical management of those toxicities is in place such that they are controlled per standard of care (e.g., grade 2 hypothyroidism requiring oral thyroid replacement).
- Participants with treated brain metastases are eligible if clinically appropriate follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
- Participants positive for human immunodeficiency virus (HIV) are eligible if they are compliant with appropriate anti-retroviral therapy for at least 6 months, have HIV viral load <400 copies/mL, and a CD4 count > 350 cells/microliter at screening.
- Participants positive for Hepatitis C virus (HCV) are eligible if they have completed definitive anti-viral therapy and have an undetectable viral load.
- Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device [IUD], surgical sterilization) at study entry and up to 6 months after the last dose of the study drug(s).
- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after study treatment discontinuation.
- Participants must have lesion(s) accessible for biopsy (other than used for measurement of disease) and be willing to undergo mandatory study biopsies in the phase 1 portion of the study. Lesions to be biopsied will be determined safely accessible by the provider performing the biopsy (e.g. interventional radiology if a liver or lung biopsy) prior to performing the biopsy. Note: If Phase 2 opens, per the investigator s discretion, if biopsy is strenuous to obtain, e.g., no easily accessible lesions are available or the subject
- condition is not amenable for biopsy, then the subject will be eligible for enrollment without biopsy at screening and for continuation of treatment without on-treatment study biopsy.
- -Participants must be able to understand and willing to sign a written informed consent document.
Who cannot join
- Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior therapeutic radiotherapy within 14 days prior to study treatment initiation.
- Participants with palliative radiotherapy performed within 7 days prior to study treatment initiation.
- Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent) with the exception of:
- intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections in participants with asthma
- using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption
- brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy).
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- Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Participants with chronic post-radiation pulmonary changes/scarring that is asymptomatic are eligible.
- Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 8 days prior to treatment initiation. Participants who have had appropriate antibiotics initiated but are still completing the treatment course are eligible if clinically improved or had minimal symptoms at presentation (e.g., urinary tract infection or pharyngeal streptococcal infection without evidence of systemic inflammatory response).
- History of organ transplant, including allogeneic stem cell transplantation.
- Participants who experienced immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy was recommended (per product label or consensus guidelines) or any immune-related toxicity requiring systemic corticosteroids (with the exception of endocrinopathy that is well controlled on replacement hormones).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.
- Receipt of a live vaccine within 28 days prior to treatment initiation. Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.
- History of infection with Hepatitis B virus (HBV) unless on suppressive therapy. Individuals with serologic evidence of a resolved prior HBV infection (i.e., HBsAgnegative and anti-HBc positive) are eligible.
- Pregnancy confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
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
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NCIMO Referral, Not Listed, NCIMO_Referrals@mail.nih.gov
National Cancer Institute Referral Office, (888) 624-1937
About this study
Background:
Each year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years.
Read more
Objective:
To test the ability of a combination of up to 4 experimental anti-cancer drugs treat mCRC. The names of these drugs are retifanlimab, TriAdeno vaccine, N-803, and SX-682. They are described below.
Eligibility:
Adults aged 18 years or older with mCRC. Participants must have
Design:
Participants will be screened. This includes having a physical exam, blood tests, urine tests, and imaging tests. If signed on to the study, participants will have 2 tumor biopsies. One when starting the study and once about 8 weeks after bring on the study. Participants will receive $500 for each biopsy.
Participants will be treated with either 3 or 4 drugs and will receive a detailed calendar explaining when each drug is given.
Retifanlimab is given every 4 weeks through an IV (an IV is tube attached to a needle inserted into a vein in the arm). N-803 is injected under the skin on the abdomen every 4 weeks.
TriAdeno vaccine is injected under the skin of the upper arm or thigh once a month for 3 doses and then once every 3 months.
Some participants will also receive a 4th drug. SX-682 is a pill taken by mouth. Participants will take this drug 2 times a day at home for about 3 weeks of each month.
Study treatment will continue up to 2 years. Follow-up phone calls/emails may continue for 3 more years.
Read the detailed description
Background:
- mCRC is incurable and available standard therapies offer a median overall survival of approximately 2 years.
- Most cases (approximately 95%) of mCRC have an intact expression of DNA mismatch repair enzymes (MLH1, MSH2, MSH6, and PMS2), and are commonly classified as having mismatch repair proficient (pMMR) or microsatellite stable (MSS) mCRC.
- MSS mCRC does not respond to immune checkpoint inhibitor (ICI) therapy whereas mismatch repair deficient (or microsatellite instability-high) mCRC is responsive to ICI therapy.
- Preclinical and clinical studies conducted at the NCI in the Laboratory of Tumor Immunology Biology (LTIB) indicate that the combination of programmed cell death protein 1 (PD-1) / Programmed death-ligand 1 (PD-L1) blockade, tumor-associated antigens (TAA) targeted vaccine, IL15 agonist, and CXCR1/2 inhibition may include sufficient immune enhancements to produce anti-tumor activity in MSS mCRC.
- Retifanlimab is a humanized IgG4 monoclonal antibody that targets PD-1. Retifanlimab has been studied in several clinical trials, and several malignancies, and has a safety and clinical activity profile similar to approved anti-PD-1 therapies (e.g., pembrolizumab).
- The TriAdeno Vaccine employs 3 adenovirus serotype 5 vectors, encoding three TAAs (CEA, MUC1, and brachyury). These vaccines have completed the phase 1 study and are safe and well tolerated. Vaccination generates antigen-specific T cell responses to CEA, MUC1, and brachyury.
- N-803 is an IL-15 agonist that activates and expands T cells and NK cells. N-803 enhances anti-tumor activity in combination with tumor-targeted vaccines. Clinically, multiple studies have demonstrated the safety of tumor-targeted vaccine in combination with PD- 1/PD-L1 blockade. Adding N-803 to PD-1/PD-L1 blockade can produce antitumor responses in disease states where responses to PD-1/PD-L1 alone would not be expected.
- SX-682 is a small molecule, orally bioavailable, allosteric antagonist of the chemokine receptors CXCR1 and CXCR2. Inhibition of CXCR1 and CXCR2 addresses a major component of intratumoral T cell suppression by myeloid-derived suppressor cells and tumor-associate macrophages. SX-682 has shown to be tolerable in combination with PD- 1/PD-L1 blockade.
Objectives:
- Phase I: to describe the safety profile of the Immuno-Oncology (IO) regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N- 803, SX 682 (A2) in participants with metastatic colorectal cancer (mCRC).
- Phase II: to determine the objective response rate (ORR) (complete response (CR) + partial response (PR)) of the IO regimen in mCRC.
Eligibility:
- Age >=18 years.
- Previously treated metastatic colorectal cancer with measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
- Adequate organ function.
Design:
- This is an open-label Phase I/II trial to evaluate the safety and efficacy of the Immuno- Oncology regimen, consisting of retifanlimab, TriAdeno vaccine, N-803, and SX-682 in participants with mCRC.
- During Phase I, we will assess the safety of the three- and the four-drug IO regimens.
- Phase II uses a Simon optimal two-stage design at SX-682 200 mg BID. Enrollment at 200 mg BID begins with a safety lead-in of 5 to 6 DLT-evaluable participants. Provided the predefined safety criteria are met (0 DLTs among the first 5 participants or <=1 DLT among the first 6), accrual will continue without interruption until a total of 9 responseevaluable participants have been treated with the four drug regimen with SX-682 at 200 mg BID. Participants enrolled during the safety lead-in who are response-evaluable will count toward the Stage 1 total of 9.
- If 0 to 1 confirmed responses (CR+PR by RECIST v1.1 within 24 weeks) are observed among these 9 participants, accrual will stop for futility. If >=2 responses are observed, enrollment will expand to a total of 23 response-evaluable participants at 200 mg BID.
- Participants will receive treatment in cycles consisting of 28 (+7) days for 2 years.
- To allow for a small number of inevaluable participants, and screen failures the accrual ceiling will be set at 60.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Retifanlimab, Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform, N-803, SX-682
- Keywords
- Monoclonal Antibody, Brachyury, MUC-1, Immunoglobulin G cytokine fusion protein, chemokine antagonist, Small Molecule
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RetifanlimabDrug
500 mg infused via IV over 30 minutes every 28 days
Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine PlatformBiological
5x10^11 virus particles per 1 mL administered via subcutaneous injection in the upper arm and anterolateral upper thigh on Day 1 of Cycles 1, 2, 3 and every 3 cycles after that
N-803Drug
15 ug/kg administered via subcutaneous injection to the abdomen every 28 days
SX-682Drug
200 mg administered orally twice per day on days 6-26 of every cycle
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Retifanlimab + TriAdeno Vaccine + N-803 Receives: Drug: Retifanlimab; Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform; Drug: N-803 |
| Arm 2 | Experimental | Retifanlimab + TriAdeno Vaccine + N-803 + SX-682 Receives: Drug: Retifanlimab; Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform; Drug: N-803; Drug: SX-682 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Safety profiles of the IO regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N-803, SX-682 (A2) in participants with metastatic colorectal cancer
Number of DLTs within DLT period (C1 days 1-28). Any toxicities identified.
Measured: Day 1 of Cycle 1 through 30 days after the last study drug administration
Phase II: Overall response rate (ORR) defined as the CR+PR of the IO regimen in mCRC
The fraction of participants with a CR or PR (per RECIST v1.1) in Phase II will be reported along with a 95% confidence interval.
Measured: Every 8 weeks until either disease progression or 2 years after initiation of study therapy.
Secondary outcomes (4)
Progression Free Survival (PFS) at 6, 12, and 24 months
PFS will be determined by the Kaplan-Meier method and reported at 6, 12, and 24 months from the date the participant was enrolled in the trial, along with 95 percent confidence intervals at these times.
Measured: Every 8 weeks until disease progression or for 2 years after initiation of study therapy
Disease control rate (DCR) at 6 and 12 months
DCR at 6 and 12 months will be reported as a fraction along with a 95 percent confidence interval for each.
Measured: Every 8 weeks until disease progression or 1 year after initiation of study therapy
Safety during Phase II
AEs will be reported by type and grade within Phase II.
Measured: From Day 1 to 30 days of the last study drug administration
Overall survival
Monitoring of participants from Day 1 of each cycle, at follow up visits and until date of death/closure of the study.
Measured: Up to 2 years after start of study therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2023
- Study start26 Mar 2024
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nicholas P Tschernia, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06149481
- Sponsor's protocol ID
- 10001563
- Other IDs
- 001563-C
- Status last verified
- 13 Oct 2026
- First submitted
- 28 Nov 2023
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC)
- ClinicalTrials.gov ID
- NCT06149481
- Acronym / sponsor ID
- 10001563
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Monoclonal Antibody, Brachyury, MUC-1, Immunoglobulin G cytokine fusion protein, chemokine antagonist, Small Molecule
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 26 Mar 2024 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2030 (estimated)
- First posted
- 29 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Each year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years.
Objective:
To test the ability of a combination of up to 4 experimental anti-cancer drugs treat mCRC. The names of these drugs are retifanlimab, TriAdeno vaccine, N-803, and SX-682. They are described below.
Eligibility:
Adults aged 18 years or older with mCRC. Participants must have
Design:
Participants will be screened. This includes having a physical exam, blood tests, urine tests, and imaging tests. If signed on to the study, participants will have 2 tumor biopsies. One when starting the study and once about 8 weeks after bring on the study. Participants will receive $500 for each biopsy.
Participants will be treated with either 3 or 4 drugs and will receive a detailed calendar explaining when each drug is given.
Retifanlimab is given every 4 weeks through an IV (an IV is tube attached to a needle inserted into a vein in the arm). N-803 is injected under the skin on the abdomen every 4 weeks.
TriAdeno vaccine is injected under the skin of the upper arm or thigh once a month for 3 doses and then once every 3 months.
Some participants will also receive a 4th drug. SX-682 is a pill taken by mouth. Participants will take this drug 2 times a day at home for about 3 weeks of each month.
Study treatment will continue up to 2 years. Follow-up phone calls/emails may continue for 3 more years.
Detailed description
Background:
- mCRC is incurable and available standard therapies offer a median overall survival of approximately 2 years.
- Most cases (approximately 95%) of mCRC have an intact expression of DNA mismatch repair enzymes (MLH1, MSH2, MSH6, and PMS2), and are commonly classified as having mismatch repair proficient (pMMR) or microsatellite stable (MSS) mCRC.
- MSS mCRC does not respond to immune checkpoint inhibitor (ICI) therapy whereas mismatch repair deficient (or microsatellite instability-high) mCRC is responsive to ICI therapy.
- Preclinical and clinical studies conducted at the NCI in the Laboratory of Tumor Immunology Biology (LTIB) indicate that the combination of programmed cell death protein 1 (PD-1) / Programmed death-ligand 1 (PD-L1) blockade, tumor-associated antigens (TAA) targeted vaccine, IL15 agonist, and CXCR1/2 inhibition may include sufficient immune enhancements to produce anti-tumor activity in MSS mCRC.
- Retifanlimab is a humanized IgG4 monoclonal antibody that targets PD-1. Retifanlimab has been studied in several clinical trials, and several malignancies, and has a safety and clinical activity profile similar to approved anti-PD-1 therapies (e.g., pembrolizumab).
- The TriAdeno Vaccine employs 3 adenovirus serotype 5 vectors, encoding three TAAs (CEA, MUC1, and brachyury). These vaccines have completed the phase 1 study and are safe and well tolerated. Vaccination generates antigen-specific T cell responses to CEA, MUC1, and brachyury.
- N-803 is an IL-15 agonist that activates and expands T cells and NK cells. N-803 enhances anti-tumor activity in combination with tumor-targeted vaccines. Clinically, multiple studies have demonstrated the safety of tumor-targeted vaccine in combination with PD- 1/PD-L1 blockade. Adding N-803 to PD-1/PD-L1 blockade can produce antitumor responses in disease states where responses to PD-1/PD-L1 alone would not be expected.
- SX-682 is a small molecule, orally bioavailable, allosteric antagonist of the chemokine receptors CXCR1 and CXCR2. Inhibition of CXCR1 and CXCR2 addresses a major component of intratumoral T cell suppression by myeloid-derived suppressor cells and tumor-associate macrophages. SX-682 has shown to be tolerable in combination with PD- 1/PD-L1 blockade.
Objectives:
- Phase I: to describe the safety profile of the Immuno-Oncology (IO) regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N- 803, SX 682 (A2) in participants with metastatic colorectal cancer (mCRC).
- Phase II: to determine the objective response rate (ORR) (complete response (CR) + partial response (PR)) of the IO regimen in mCRC.
Eligibility:
- Age >=18 years.
- Previously treated metastatic colorectal cancer with measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
- Adequate organ function.
Design:
- This is an open-label Phase I/II trial to evaluate the safety and efficacy of the Immuno- Oncology regimen, consisting of retifanlimab, TriAdeno vaccine, N-803, and SX-682 in participants with mCRC.
- During Phase I, we will assess the safety of the three- and the four-drug IO regimens.
- Phase II uses a Simon optimal two-stage design at SX-682 200 mg BID. Enrollment at 200 mg BID begins with a safety lead-in of 5 to 6 DLT-evaluable participants. Provided the predefined safety criteria are met (0 DLTs among the first 5 participants or <=1 DLT among the first 6), accrual will continue without interruption until a total of 9 responseevaluable participants have been treated with the four drug regimen with SX-682 at 200 mg BID. Participants enrolled during the safety lead-in who are response-evaluable will count toward the Stage 1 total of 9.
- If 0 to 1 confirmed responses (CR+PR by RECIST v1.1 within 24 weeks) are observed among these 9 participants, accrual will stop for futility. If >=2 responses are observed, enrollment will expand to a total of 23 response-evaluable participants at 200 mg BID.
- Participants will receive treatment in cycles consisting of 28 (+7) days for 2 years.
- To allow for a small number of inevaluable participants, and screen failures the accrual ceiling will be set at 60.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Retifanlimab, Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform, Drug: N-803Retifanlimab + TriAdeno Vaccine + N-803 |
| Arm 2 | Experimental | Drug: Retifanlimab, Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform, Drug: N-803, Drug: SX-682Retifanlimab + TriAdeno Vaccine + N-803 + SX-682 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants with histologically confirmed colorectal cancer and evidence of metastatic disease.
- Participants must have received, been ineligible to receive, or refused to receive two lines of standard systemic therapy i.e., a fluoropyrimidine with oxaliplatin or irinotecan with bevacizumab, regorafenib, trifluridine, and (if history of RAS wild-type) EGFR-targeted therapy. Participants must have received one line of systemic checkpoint inhibitor if history of advanced microsatellite instability-high [MSI-H/dMMR]) metastatic colon cancer.
- Participants who had progressive disease within 6 months before study treatment following standard adjuvant therapy are eligible if they have not received systemic therapy for metastatic disease. Participants with a history of MSI-H/dMMR must have also received one line of checkpoint inhibitor therapy.
- Age >= 18 years.
- Measurable disease per RECIST 1.1.
Key exclusion criteria (15 listed)
- Participants with prior investigational drug, chemotherapy, immunotherapy, or any prior therapeutic radiotherapy within 14 days prior to study treatment initiation.
- Participants with palliative radiotherapy performed within 7 days prior to study treatment initiation.
- Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent) with the exception of:
- Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Participants with chronic post-radiation pulmonary changes/scarring that is asymptomatic are eligible.
- Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 8 days prior to treatment initiation. Participants who have had appropriate antibiotics initiated but are still completing the treatment course are eligible if clinically improved or had minimal symptoms at presentation (e.g., urinary tract infection or pharyngeal streptococcal infection without evidence of systemic inflammatory response).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retifanlimab500 mg infused via IV over 30 minutes every 28 days | Drug | Arm 1, Arm 2 |
| Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform5x10^11 virus particles per 1 mL administered via subcutaneous injection in the upper arm and anterolateral upper thigh on Day 1 of Cycles 1, 2, 3 and every 3 cycles after that | Biological | Arm 1, Arm 2 |
| N-80315 ug/kg administered via subcutaneous injection to the abdomen every 28 days | Drug | Arm 1, Arm 2 |
| SX-682200 mg administered orally twice per day on days 6-26 of every cycle | Drug | Arm 2 |
Primary outcome
Phase I: Safety profiles of the IO regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N-803, SX-682 (A2) in participants with metastatic colorectal cancer
Time frame: Day 1 of Cycle 1 through 30 days after the last study drug administration
Number of DLTs within DLT period (C1 days 1-28). Any toxicities identified.
Phase II: Overall response rate (ORR) defined as the CR+PR of the IO regimen in mCRC
Time frame: Every 8 weeks until either disease progression or 2 years after initiation of study therapy.
The fraction of participants with a CR or PR (per RECIST v1.1) in Phase II will be reported along with a 95% confidence interval.
4 secondary outcomes
Progression Free Survival (PFS) at 6, 12, and 24 months
Time frame: Every 8 weeks until disease progression or for 2 years after initiation of study therapy
Disease control rate (DCR) at 6 and 12 months
Time frame: Every 8 weeks until disease progression or 1 year after initiation of study therapy
Safety during Phase II
Time frame: From Day 1 to 30 days of the last study drug administration
Overall survival
Time frame: Up to 2 years after start of study therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All collected IPD will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicholas P Tschernia, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Retifanlimab, Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform and N-803 in people with Metastatic Colorectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NCI Referral Office ((888) 624-1937, ncimo_referrals@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Safety profiles of the IO regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N-803, SX-682 (A2) in participants with metastatic colorectal cancer (time frame: Day 1 of Cycle 1 through 30 days after the last study drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.