Treatment for advanced pancreatic cancer using engineered immune cells

Phase I/II Study of Anti-CD3 x Anti-EGFR Bispecific Antibody (EGFRBi) Armed Fresh Peripheral Blood Mononuclear Cells (EGFR FPBMC) in Metastatic or Unresectable Pancreatic Cancer

This study is testing a new treatment that uses specially modified immune cells to see if it can help people with advanced pancreatic cancer feel better and fight their disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Virginia (Academic / other)
• Drugs / interventions: cetuximab, chemotherapy, immunotherapy
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT06479239 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of a novel treatment combining bispecific antibodies with fresh peripheral blood mononuclear cells (PBMC) in patients with metastatic or unresectable pancreatic cancer. Eligible participants will undergo a leukapheresis procedure to collect their white blood cells, which will then be treated to enhance their ability to target and destroy cancer cells. Following this, patients will receive a series of intravenous infusions of the engineered immune cells over several weeks, with regular monitoring of their disease status and immune response throughout the treatment period.

Who should consider this trial

Good fit: Ideal candidates include adults with histologically confirmed locally advanced or metastatic pancreatic cancer who have previously received chemotherapy and have stable disease.

Not a fit: Patients with pancreatic cancer that is resectable or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced pancreatic cancer who have limited treatment choices.

How similar studies have performed: While this approach is innovative, similar studies using engineered immune cells have shown promise in other cancers, suggesting potential for success in this context.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed locally advanced pancreatic cancer (LAPC)/unresectable pancreatic cancer (UPC) or metastatic pancreatic cancer (MPC) not eligible for curative intent therapy
2. Received at least 1 line of chemotherapy and have stable disease (SD) or better for 3 months prior to enrollment. Therapy should consist of either a gemcitabine, 5FU-based (including capecitabine) or albumin-bound paclitaxel-based regimen. Patients with actionable mutations should have received targeted therapy prior to enrollment on trial. Patients who qualify for immunotherapy due to mismatch repair protein/microsatellite stable and tumor mutational burden status should also have received immunotherapy prior to enrollment on trial.
3. Measurable disease by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
5. Age ≥ 18 years
6. Females of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment/registration
7. Females of childbearing potential and males must agree to use an effective method for contraception for the duration of the treatment with study drug plus 90 days (duration of sperm turnover). Males must also abstain from sperm donations during study treatment and for at least 90 days after the last dose of study drug.
8. Adequate organ function within 14 days prior to registration, defined as the following:

   * Absolute neutrophil count \>= 500/mm3
   * Absolute lymphocyte count \>= 400/mm3
   * Platelets \>= 75,000/mm3
   * Hemoglobin \>= 8 g/dL
   * Serum creatinine \< 2.0mg/dL or calculated/measured creatinine clearance \>= 50 ml/min
   * Bilirubin \<= 2 mg/dL
   * Aspartate transferase (AST) and Alanine transaminase (ALT) \<= 5.0 x upper limit of normal (ULN)
   * Alpha gal \< 0.35 IU/ml or "negative"
9. Ability to provide informed consent and provision of written informed consent
10. Stated willingness to comply with all study procedures and availability for the duration of the study
11. Adequate cardiac function as defined as:

    * No uncontrolled angina or severe ventricular arrhythmias
    * No clinically significant pericardial disease
    * No history of myocardial infarction (MI) in the last year before registration
    * No Class 3 or higher New York Heart Association Congestive Heart Failure

Exclusion Criteria:

1. Known hypersensitivity to cetuximab
2. Treatment with investigational agent within 3 weeks prior to registration
3. Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration
4. Known active liver disease, human immunodeficiency virus (HIV)+ or evidence of active Hepatitis C or B virus; bleeding or condition associated with high-risk bleeding (anticoagulation is allowed)
5. Active infection; prior antibiotic/antifungal/antiviral therapies within 2 weeks prior to registration
6. History of a myocardial infarction within 1 year prior to registration
7. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
8. Autoimmune disease that has required systemic treatment with chronic steroids or immunosuppressive therapy in the 2 years prior to registration (thyroxine, insulin, or corticosteroid replacement is allowed)
9. History or evidence of any condition that might confound the results of the trial, interfere with the subject's participation, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
10. Females must not be currently breast feeding.
11. The treating investigator feels the patient is not able to be compliant.
12. History of active Bacillus Tuberculosis (TB).
13. Has received a live vaccine within 30 days of registration.
14. Prisoners or patients who are incarcerated.
15. Patients who are compulsorily detained for treatment of a psychiatric or physical illness.

Where this trial is running

Charlottesville, Virginia

• University of Virginia — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Tri Le, MD, DSc — University of Virginia
• Study coordinator: Ashley Donihee

Conditions Pancreas Cancer; Pancreatic Cancer