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)
National Cancer Institute (NCI)
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.
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 t…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* 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 prog…
Interventions
- DrugRetifanlimab
500 mg infused via IV over 30 minutes every 28 days
- BiologicalTherapeutic 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
- DrugN-803
15 ug/kg administered via subcutaneous injection to the abdomen every 28 days
- DrugSX-682
100 mg administered orally twice per day on days 6-26 of every cycle
Location
- National Institutes of Health Clinical CenterBethesda, Maryland