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)

Plain English Summary

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) is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Metastatic Colorectal Cancer. This trial tests a combination of up to four experimental drugs to treat advanced colorectal cancer that has spread to other organs. It is for adults aged 18 and older with metastatic colorectal cancer who have previously received standard treatments. Participation involves regular clinic visits for drug infusions, injections, and oral medication, along with biopsies and imaging scans. Alternative treatments include chemotherapy, targeted therapy, and other immunotherapies, depending on prior treatments and disease characteristics. The trial aims to enroll 60 participants.

Official 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. ...

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 or older with colorectal cancer that has spread. Must have received at least two prior standard treatments for advanced disease, or one if they have a specific genetic marker (MSI-H/dMMR) and have had prior immunotherapy. Must have measurable disease and good organ function (blood counts, liver, and kidney function within certain limits). Cannot have active autoimmune disease requiring significant steroid treatment or active infections. This trial is studying Metastatic Colorectal Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures assess how safe the combination of drugs is and how well it shrinks tumors, which indicates how effective the treatment might be in controlling the cancer. The specific primary outcome measures are: 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 (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 (Every 8 weeks until either disease progression or 2 years after initiation of study therapy.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to address the significant unmet need in metastatic colorectal cancer by exploring a novel combination of immunotherapies that may offer a new treatment option for patients with limite Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic Colorectal Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant patient population with limited treatment options, representing a potential advancement in immunotherapy for a common cancer, with the National Cancer Institute as a s Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, potential side effects, and how this combination might differ from other treatments you've had. Be prepared for regular clinic visits for infusions and injections, and to take oral medication at home. You will undergo biopsies at the start and during the study, for which you will be compensated. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 60 participants

Interventions

• 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 Outcomes

• 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 (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 (Every 8 weeks until either disease progression or 2 years after initiation of study therapy.)

Secondary Outcomes

• 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)

Full Eligibility 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.
* 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.

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

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Frequently Asked Questions

Related Conditions

• Colorectal Cancer
• Metastatic Cancer
• Gastrointestinal Cancers
• Oncology
• Immunotherapy
• Cancer Vaccines
• Checkpoint Inhibitors
• Targeted Therapy
• Drug Combinations
• Clinical Trials

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