Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer

Phase 1b/2 Study of Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer

By doing this study, it is the hope to learn whether an injection of the measles, mumps, rubella (MMR) vaccine developed by Merck & Co. (Merck's M-M-R® II) into the tumor is safe and effective in making the tumor smaller.

Study Overview

• Status: Not yet recruiting
• Conditions: Borderline Resectable/Unresectable Pancreatic Cancer; Non Metastatic Pancreatic Cancer
• Intervention / Treatment: Biological: Intratumoral MMR Injection

Detailed Description

This is a prospective single-arm phase Ib/II study for subjects with locally advanced, borderline resectable / unresectable, non-metastatic pancreatic cancer that remains unresectable following SoC chemotherapy and RT. Patients whose tumors have not become resectable following SoC treatment with chemotherapy and RT will be treated with intratumoral injection of MMR vaccine by endoscopy and endoscopic ultrasound. Patients with unresectable or borderline resectable pancreatic cancer treated via SoC protocol with induction chemotherapy (of physician's choice, e.g., FOLFIRINOX, Gemcitabine + Abraxane, Nab Paclitaxel or NALIRIFOX) followed by radiation (physician's preference) along with chemotherapy (5FU/capecitabine, per physician's choice) will be eligible for the study if the tumor did not become resectable following the therapy just described.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Joseph Holley, BS; Phone Number: 24579 501-214-2499; Email: JAHolley@uams.edu
• Study Contact Backup: Name: Jennifer Faulkner, MS; Phone Number: 24544 501-214-2499; Email: JLFaulkner@uams.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Pathologically proven locally advanced adenocarcinoma of pancreas.

3. Borderline resectable pancreatic cancer that is determined to be unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following:

   1. Encasement of gastroduodenal artery up to the common hepatic artery/short segment encasement or abutment of the hepatic artery, but without extension to the celiac trunk.
   2. Venous involvement of SMV or portal vein, less than 180 degrees.

   3. Tumor abutment of SMA, less than half the circumference of the vessel wall. OR

      Unresectable pancreatic cancer that remains unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following:

   4. Greater than 180-degree encasement or occlusion/thrombus of SMA, unresectable SMV, or SMV-portal confluence occlusion.
   5. Direct involvement of inferior vena cava, aorta, celiac trunk, or hepatic artery, as defined by the absence of fat plane between low-density tumor and these structures on CT scan.

   OR Surgeon deems that the pancreatic cancer is unresectable.

4. Prior history of treatment with chemotherapy (e.g., FOLFIRINOX, Gemcitabine + Abraxane or NALIRIFOX [liposomal irinotecan (Nal-IRI or Onivyde®), Nab Paclitaxel, 5 fluorouracil (5-FU)/leucovorin and oxaliplatin]) and RT. The chemotherapy regimen is per treating physician's choice. The chemotherapy agent for radio sensitization is up to the treating physician (capecitabine, 5FU or gemcitabine).

   a. The chemo-radiation therapy regimen should be completed at least 6 weeks but no more than 12 weeks from planned Day 1.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Adequate hematological function (Hemoglobin > 9g/dL, White Blood Cell (WBC) count > 1500 K/µL, Absolute Neutrophil Count (ANC) > 500 K/µL, Platelet count > 100 K/µL).
7. Adequate hepatic function (Total bilirubin ≤ 1.5 x institutional upper limit of normal [ULN]) (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 × ULN, subject is eligible); Aspartate aminotransferase (AST[SGOT]) or Alanine aminotransferase (ALT[SGPT]) ≤ 2.5 × institutional ULN; Serum albumin ≥ 3.0 g/dL.
8. Adequate renal function (i.e., creatinine less than 1.5 times ULN).

Exclusion Criteria:

1. Pancreatic cancer that was either resectable before SoC treatment or became resectable following SoC chemotherapy and RT.
2. Subjects with radiographically proven metastatic disease are excluded.
3. Subject must not be pregnant and/or currently breastfeeding or plan to be.
4. Subject must not have received any live vaccine, including MMR, within 30 days prior to the dose of study drug.
5. Subject must not have treatment with any anti-cancer therapy including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents, within 5 half-lives (or 2 weeks if half-life is unknown) prior to day 1.
6. Subject has no unresolved toxicities, AEs ≥ Grade 2 (NCI CTCAE version 5.0), from prior anticancer therapy.
7. Any other condition that, in the opinion of the investigator, might interfere with the safe conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intratumoral MMR Injection	Biological: Intratumoral MMR Injection; A single dose (0.5 mililiter) of MMR vaccine will be injected under endoscopic ultrasound guidance in the GI laboratory at UAMS under sedation as prescribed by the interventional gastroenterologist. The injection will be at least 6 weeks but no later than 12 weeks post completion of chemo-radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intratumoral T-Cell Response	Intratumoral T-cell Response (iTCR) will be defined as a change of greater than 2-fold increase in the frequency of IFNγ-positive T- cells in the repeat (4 week) tumor biopsy relative to the first (baseline) tumor biopsy. Each subject will be scored Yes or No for if they achieved iTCR. Subjects that decline the repeat tumor biopsy will be scored Not Evaluable (NE) for iTCR.	Baseline to 4 weeks post injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The clinical efficacy of MMR vaccines will be assessed according to RECIST 1.1	A subject's Progression Free Survival (PFS) will be defined as the time in months from the date when their tumor is injected with MMR vaccine to the date on which they either die or experience documented progressive disease (whichever occurs first). Subjects that are alive and progression-free on their date of at last contact will be right-censored for PFS. A subject's Overall Survival will be defined as the time in months from the date when their tumor is injected with MMR vaccine to the date on which they die. Subjects that are still alive at last contact will be right censored for OS.	At screening and every 12 weeks from day 1 for 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response dynamics following treatment with MMR	T cell function will be at screening, Day 1, Day 8, Week 4 and Week 8 using PBMCs isolated from subject samples. Functional assays will include flow cytometry to assess T cell subsets including CD4 and CD8 T cells along with activation markers like CD69 and CD25. Markers of T cell exhaustion such as PD1, CTLA4, LAG3, VISTA and TIM3 will be analyzed to assess immune dysfunction and potential resistance to treatment. Intracellular cytokine staining will measure IFN gamma TNF alpha and IL2 production as indicators of immune response. ELISPOT assays will quantify antigen specific T cell responses while proliferation assays using CFSE dilution will evaluate T cell expansion. RNA sequencing and multiplex cytokine profiling will help characterize transcriptional and secretory profiles related to T cell activation exhaustion and memory formation. The FNA samples will used to study gene signatures	From MMR injection to week 8

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Rangaswamy Govindarajan, MD, University of Arkansas

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; MMR; Borderline Resectable; Non-Metastatic; Borderline Unresectable
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 298471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified clinical and biochemical data derived from human subjects enrolled in the phase I study evaluating intratumoral administration of the MMR vaccine in patients with locally advanced, borderline resectable, or unresectable non-metastatic pancreatic cancer following standard-of-care chemotherapy and radiation therapy. The dataset will include patient demographic information (de-identified), treatment details, safety outcomes, imaging-based tumor response assessments, immune profiling data (e.g., T-cell response measurements), and circulating tumor DNA (ctDNA) analyses. The data will be generated from approximately 20 subjects enrolled under the study protocol titled "Phase 1b/2 Study of Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer." All data will be de-identified prior to sharing and transmitted securely via Box for the purposes of collaborative analysis, manuscript preparation, and grant develop
• IPD Sharing Time Frame: The IPD and supporting information will be available from the trials starting date until the professor leaves the institution.
• IPD Sharing Access Criteria: Specific researchers that are listed in the data transfer agreement will be able to access the dataset which will include patient demographic information (de-identified), treatment details, safety outcomes, imaging-based tumor response assessments, immune profiling data (e.g., T-cell response measurements), and circulating tumor DNA (ctDNA) analyses. They will access this dataset via institutional BOX access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No