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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)

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ClinicalTrials.gov Identifier: NCT06149481
Recruitment Status : Recruiting
First Posted : November 29, 2023
Last Update Posted : March 29, 2024
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Retifanlimab Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform Drug: N-803 Drug: SX-682 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 26, 2024
Estimated Primary Completion Date : October 31, 2025
Estimated Study Completion Date : October 31, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Arm 1
Retifanlimab + TriAdeno Vaccine + N-803
Drug: Retifanlimab
500 mg infused via IV over 30 minutes every 28 days

Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform
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

Drug: N-803
15 ug/kg administered via subcutaneous injection to the abdomen every 28 days

Experimental: Arm 2
Retifanlimab + TriAdeno Vaccine + N-803 + SX-682
Drug: Retifanlimab
500 mg infused via IV over 30 minutes every 28 days

Biological: Therapeutic CEA, Brachyury and MUC1 TriAdeno Vaccine Platform
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

Drug: N-803
15 ug/kg administered via subcutaneous injection to the abdomen every 28 days

Drug: SX-682
100 mg administered orally twice per day on days 6-26 of every cycle




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    DCR at 6 and 12 months will be reported as a fraction along with a 95 percent confidence interval for each.

  3. Safety during Phase II [ Time Frame: From Day 1 to 30 days of the last study drug administration ]
    AEs will be reported by type and grade within Phase II.

  4. Overall survival [ Time Frame: Up to 2 years after start of study therapy ]
    Monitoring of participants from Day 1 of each cycle, at follow up visits and until date of death/closure of the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION 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.
  • Women of child-bearing potential (WOCBP) and men 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.

EXCLUSION CRITERIA:

  • 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 WOCBP at screening.
  • Uncontrolled intercurrent illness that would limit compliance with study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06149481


Contacts
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Contact: NCI Referral Office 1-888-NCI-1937 ncimo_referrals@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: NCIMO Referral    Not Listed    NCIMO_Referrals@mail.nih.gov   
Contact: National Cancer Institute Referral Office    (888) 624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jason M Redman, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT06149481    
Other Study ID Numbers: 10001563
001563-C
First Posted: November 29, 2023    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 22, 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data from this study may be requested from other researchers within 10 years after the completion of the primary endpoint. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: Data from this study may be requested by contacting the PI. Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Monoclonal Antibody
Brachyury
MUC-1
Immunoglobulin G cytokine fusion protein
chemokine antagonist
Small Molecule
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases