Miami EMPIRE: Eradication of Metastatic Pancreatic Cancer with Immuno-Radiation

A Phase 2 Single Arm Trial of Stereotactic Body Radiation Therapy Followed by Dual Immune Checkpoint Inhibition for Patients With Metastatic Pancreatic Ductal Adenocarcinoma - The Miami "EMPIRE" Trial - Eradication of Metastatic Pancreatic Cancer With Immuno-Radiation

This trial will try adding targeted radiation to two immune checkpoint drugs, botensilimab and balstilimab, for adults with metastatic pancreatic ductal adenocarcinoma who progressed after at least one prior systemic therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Miami (Academic / other)
• Drugs / interventions: balstilimab, botensilimab, chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT06843551 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial combines stereotactic body radiation therapy (SBRT) with two immune checkpoint antibodies, botensilimab and balstilimab, to stimulate anti-tumor immune responses in metastatic pancreatic ductal adenocarcinoma. Eligible patients have measurable, microsatellite-stable disease and have progressed on one or more lines of systemic therapy. Patients will receive SBRT to selected tumor sites alongside scheduled infusions of both immunotherapy agents, and investigators will monitor tumor response by RECIST 1.1 criteria and track safety and immune-related adverse events. The study is conducted at the University of Miami and includes laboratory and imaging assessments before and during treatment.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with histologically confirmed, microsatellite-stable metastatic pancreatic ductal adenocarcinoma, measurable disease, ECOG 0–1, adequate blood counts, and progression after at least one prior line of systemic therapy.

Not a fit: Patients with poor performance status, active infections (such as HIV or hepatitis B), those on immunosuppressive therapy or chronic steroids, or patients who do not meet the microsatellite-stable and prior-therapy criteria are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, the combination could improve tumor control and extend survival or time without progression for patients with metastatic pancreatic cancer.

How similar studies have performed: Checkpoint inhibitors alone have shown limited benefit in microsatellite-stable pancreatic cancer, though early-phase studies combining radiation and immunotherapy in other cancers have shown promising signals, making this combination experimental in pancreatic cancer.

Eligibility criteria

Inclusion Criteria:

1. ≥18 years old
2. Histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
3. Microsatellite stable (MSS) disease by pathologic assessment.
4. Patients must have measurable disease as defined by RECIST 1.1.
5. Progression on ≥1 line of systemic therapy.
6. No concomitant therapy with any of the following: interleukin (IL)-2, interferon, non study immunotherapy regimens, cytotoxic chemotherapy, immunosuppressive agents, other investigational therapies, and/or chronic use of systemic corticosteroids.
7. No known infection with human immunodeficiency virus (HIV) or active infection with Hepatitis B.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
9. Life expectancy ≥3 months.
10. Patients must have the following lab values obtained \<4 weeks prior to starting protocol treatment:

    1. absolute neutrophil count (ANC) ≥1,000 cells/μL
    2. white blood count (WBC) ≥2,000 cells/μL
    3. platelets ≥75,000 per μL
    4. hemoglobin ≥8.0 g/dL
    5. creatinine clearance ≥40 mL/min)
    6. serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
    7. aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 × ULN (or ≤5 × ULN in patients with liver metastases)
    8. international normalized ratio or prothrombin time ≤1.5 × ULN
    9. activated partial thromboplastin time ≤2.5 × ULN
    10. absolute lymphocyte count (ALC) ≥1000 cells/μL at baseline
11. At least 1 previously unirradiated lesion amenable to pre-treatment biopsy.
12. No limit on overall numbers of lesions, but liver tumor burden ≤25% of total liver volume.
13. Women of childbearing potential (WOCBP): negative serum pregnancy test (within 7 days prior to Day 1 of protocol therapy)

    a. Females of non-childbearing potential are defined as: i. ≥ 50 years of age and has not had menses for greater than 1 year ii. Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation iii. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.
14. Male and female patients of reproductive potential must use effective methods of contraception or abstain from sexual activity for the course of the study through at least 6 months after the last dose of balstilimab and/or botensilimab. See Section 4.11, Contraception.

Exclusion Criteria:

1. Liver tumor burden exceeding 25% of total liver volume.
2. Active, untreated central nervous system (CNS) metastases.
3. Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents or immunosuppressive drugs).
4. Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mg daily prednisone equivalent) are permitted in the absence of active autoimmune disease.
5. Previous external beam radiation therapy to the liver or radioisotope therapy directed to the liver or any liver embolization.
6. Clinically significant ascites requiring a paracentesis in the last 4 weeks, or clinically significant history of liver failure defined as any prior episode of hepatic encephalopathy and/or any prior history of an elevated serum ammonia level.
7. Partial or complete bowel obstruction within the last 3 months prior to study enrollment, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
8. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of study enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.

   a. QT interval corrected using Fridericia's formula (QTcF) of \> 480 ms.
9. Prior allogeneic organ transplantation.
10. Treatment with chemotherapy or targeted therapy within 2 weeks prior to initiating EMPIRE treatment.
11. Persistent grade ≥2 adverse events (aEs) from prior therapy (except neuropathy).
12. Known additional malignancy requiring active treatment.
13. History of non-infectious pneumonitis.
14. Active infection requiring antibiotic.
15. Live vaccine within 30 days of protocol treatment.
16. Severe acute respiratory syndrome (SARS) coronavirus 2 (CoV 2) (SARS-CoV-2) vaccine or booster \< 7 days before Cycle 1 Day 1 (C1D1). For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \> 7 days from C1D1 or \> 7 days from future cycle on study.
17. History of severe hypersensitivity reaction to monoclonal antibody.
18. Participants with impaired decision-making capacity.

Where this trial is running

Miami, Florida

• University of Miami — Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Benjamin Spieler, MD — University of Miami
• Study coordinator: Benjamin Spieler, MD

Conditions Metastatic Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Cancer