The Miami "EMPIRE" Trial - Eradication of Metastatic Pancreatic Cancer With Immuno-Radiation

NCT06843551 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 20240455
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess if radiation therapy (which uses high-energy radiation to damage or destroy cancer cells) combined with immune checkpoint inhibitors (medications that helps the body recognize and attack cancer cells) will be beneficial for patients with metastatic pancreatic ductal adenocarcinoma.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  The Clinical Benefit Rate (CBR) among participants will be reported. CBR is the number of participants achieving complete response (CR), partial response (PR) or stable disease after start of study therapy. Response will be assessed using Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) 1.1 criteria.

  Up to 15 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 15 months

• Progression-Free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• Number of Participants Experiencing Grade 3 or Higher Toxicities

  Up to 15 months

Study Arms (1)

Radiation, Botensilimab Combined with Balstilimab Treatment Group

EXPERIMENTAL

Participants in this group will receive Stereotactic Body Radiation Therapy (SBRT), followed by Botensilimab immunotherapy (ImT) for up to 24 weeks, in combination with Balstilimab ImT for up to one year. Total participation duration is up to five years.

Radiation: Stereotactic Body Radiation Therapy; Drug: Botensilimab; Drug: Balstilimab

Interventions

Stereotactic Body Radiation Therapy RADIATION

The radiation therapy (RT) prescription biologically effective dose (BED10) goal for tumor (α/β=10) aims to achieve at least BED10= 60 Gy for a single fraction plan and at least BED10=100 Gy for a multi-fraction plan. This equates to a prescription dose of at least 20 Gy in a single fraction, 42 Gy over 3 fractions, 50 Gy over 5 fractions, and 62 Gy over 10 fractions. Radiation therapy must be completed for up to 10 daily treatments within a 15-day course.

Radiation, Botensilimab Combined with Balstilimab Treatment Group

Botensilimab DRUG

Participants will be receive 75mg of Botensilimab immunotherapy administered via intravenous infusion, every six weeks for up to 4 doses, about 24 weeks. Botensilimab therapy will begin no later than seven (7) days after completion of radiation therapy.

Radiation, Botensilimab Combined with Balstilimab Treatment Group

Balstilimab DRUG

Participants will receive 240mg of Balstilimab immunotherapy, administered via intravenous infusion, every 2 weeks for up to one (1) year. Balstilimab therapy will begin no later than seven (7) days after completion of radiation therapy.

Radiation, Botensilimab Combined with Balstilimab Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old
• Histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
• Microsatellite stable (MSS) disease by pathologic assessment.
• Patients must have measurable disease as defined by RECIST 1.1.
• Progression on ≥1 line of systemic therapy.
• 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.
• No known infection with human immunodeficiency virus (HIV) or active infection with Hepatitis B.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy ≥3 months.
• Patients must have the following lab values obtained \<4 weeks prior to starting protocol treatment:
• absolute neutrophil count (ANC) ≥1,000 cells/μL
• white blood count (WBC) ≥2,000 cells/μL
• platelets ≥75,000 per μL
• hemoglobin ≥8.0 g/dL
• creatinine clearance ≥40 mL/min)

You may not qualify if:

• Liver tumor burden exceeding 25% of total liver volume.
• Active, untreated central nervous system (CNS) metastases.
• 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).
• 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.
• Previous external beam radiation therapy to the liver or radioisotope therapy directed to the liver or any liver embolization.
• 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.
• 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.
• 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.
• Prior allogeneic organ transplantation.
• Treatment with chemotherapy or targeted therapy within 2 weeks prior to initiating EMPIRE treatment.
• Persistent grade ≥2 adverse events (aEs) from prior therapy (except neuropathy).
• Known additional malignancy requiring active treatment.
• History of non-infectious pneumonitis.
• Active infection requiring antibiotic.

Sponsors & Collaborators

• Benjamin Spieler: lead
• Agenus Inc.: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Radiosurgery; balstilimab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Benjamin Spieler, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Spieler, MD

CONTACT

305-243-4229; bxs737@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: February 25, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)