RECRUITING

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)

Conditions

Metastatic Colorectal Cancer Monoclonal Antibody Brachyury MUC-1 Immunoglobulin G cytokine fusion protein chemokine antagonist Small Molecule

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2024-03-26

Study Completion:2030-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06149481

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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. 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. * Participants must be able to understand and willing to sign a written informed consent document.	* 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). * 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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. 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.
* Participants must be able to understand and willing to sign a written informed consent document.

* 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).
* 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.

Contacts and Locations

Study Contact

NCI Referral Office

CONTACT

(888) 624-1937

ncimo_referrals@nih.gov

Principal Investigator

Nicholas P Tschernia, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Nicholas P Tschernia, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-03-26

Study Completion Date2030-10-31

Study Record Updates

Study Start Date2024-03-26

Study Completion Date2030-10-31

Terms related to this study

Keywords Provided by Researchers

Monoclonal Antibody
Brachyury
MUC-1
Immunoglobulin G cytokine fusion protein
chemokine antagonist
Small Molecule

Additional Relevant MeSH Terms

Metastatic Colorectal Cancer