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)
2 other identifiers
interventional
60
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2024
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 28, 2023
CompletedFirst Posted
Study publicly available on registry
November 29, 2023
CompletedStudy Start
First participant enrolled
March 26, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2030
May 1, 2026
November 18, 2025
3.6 years
November 28, 2023
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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.
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
Every 8 weeks until disease progression or for 2 years after initiation of study therapy
Disease control rate (DCR) at 6 and 12 months
Every 8 weeks until disease progression or 1 year after initiation of study therapy
Safety during Phase II
From Day 1 to 30 days of the last study drug administration
Overall survival
Up to 2 years after start of study therapy
Study Arms (2)
Arm 1
EXPERIMENTALRetifanlimab + TriAdeno Vaccine + N-803
Arm 2
EXPERIMENTALRetifanlimab + TriAdeno Vaccine + N-803 + SX-682
Interventions
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
Eligibility Criteria
You may qualify if:
- 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).
- +7 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nicholas P Tschernia, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 28, 2023
First Posted
November 29, 2023
Study Start
March 26, 2024
Primary Completion (Estimated)
October 31, 2027
Study Completion (Estimated)
October 31, 2030
Last Updated
May 1, 2026
Record last verified: 2025-11-18
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, 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.
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.