CAR T Cell Immunotherapy for Pancreatic Cancer

NCT03323944 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 827644 (UPCC 14217)
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I study to establish the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells in patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma

Conditions

Pancreatic Cancer; Cancer of the Pancreas

Keywords

metastatic adenocarcinoma, pancreas

Outcome Measures

Primary Outcomes (1)

• Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  2 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

• Objective response rate

  2 years

Study Arms (5)

Cohort 1: huCART-meso cells via intravenous infusion (IV).

EXPERIMENTAL

Subjects will receive a single dose of 1-3x10\^7/m\^2 lentiviral transduced huCART-meso cells on day 0 via intravenous infusion.

Biological: huCART-meso cells

Cohort -1: low dose huCART-meso cells via intravenous infusion

EXPERIMENTAL

In the event that 2 DLTs occur among subjects enrolled in Cohort 1, then enrollment in Cohort 1 will be stopped and the dose will be de-escalated by 10-fold to 1-3x10\^6 cells/m\^2. Subjects will receive a single dose of 1-3x10\^6 cells/m\^2 lentiviral transduced huCART-meso cells on day 0.

Biological: huCART-meso cells

Cohort 2 - huCART meso cells via intraperitoneal infusion (IP)

EXPERIMENTAL

Permanently closed

Biological: huCART-meso cells

Cohort 3 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)

EXPERIMENTAL

Permanently closed

Biological: huCART-meso cells

Cohort 4 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)

EXPERIMENTAL

Subjects will receive a single dose of of 1-3x10\^7 cells/m\^2 lentiviral transduced huCART-meso cells on day 0 following a minimum 1 week washout from standard care chemotherapy. This initial intrahepatic infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart.

Biological: huCART-meso cells

Interventions

huCART-meso cells BIOLOGICAL

Intravenous administration or local delivery of lentiviral transduced huCART-meso cells.

Cohort -1: low dose huCART-meso cells via intravenous infusion; Cohort 1: huCART-meso cells via intravenous infusion (IV).; Cohort 2 - huCART meso cells via intraperitoneal infusion (IP); Cohort 3 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion); Cohort 4 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)

Eligibility Criteria

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

You may qualify if:

• Patients with the following diagnoses:
• Cohorts 1 and -1: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma
• Cohort 2: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; and either cytologically-proven ascites or known peritoneal disease on radiologic imaging.
• Cohort 3 - 4: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma with liver metastases as confirmed by pathology or radiographic imaging.
• Prior treatment requirements:
• Cohorts 1 - 3: Failure of at least one prior standard of care chemotherapy for advanced stage disease.
• Cohort 4: At lease stable disease on the first-line standard of care chemotherapy for advanced stage disease.
• Cohorts 1-3 and -1: Subjects must have measurable disease as defined by RECIST 1.1 criteria.
• Patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Satisfactory organ and bone marrow function as defined by the following:
• i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 8 g/dL iv. Direct bilirubin ≤ 2.0 mg/dl unless the subject has Gilbert's disease syndrome (≤ 3.0 mg.dl) v. Creatinine ≤ 1.5x the institutional normal upper limit vi. Albumin ≥ 2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5x the institutional normal upper limit viii. Cardiac ejection fraction of ≥40% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
• Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
• Provides written informed consent.
• Subjects of reproductive potential must agree to use acceptable birth control methods

You may not qualify if:

• Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer, or prostate cancer with PSA level \< 1.0) are not excluded.
• HIV infection
• Active hepatitis B or hepatitis C infection
• Active autoimmune disease (including but not limited to: systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation by physician-investigator, with the exception of thyroid replacement.
• Patients with ongoing or active infection.
• Dependence on systemic steroids or immunosuppressant medications.
• Patients requiring supplemental oxygen therapy.
• Prior therapy with lentiviral gene modified cells.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
• Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected.
• Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to eligibility confirmation by physician-investigator is acceptable.
• Pregnant or breastfeeding women.
• Patients with significant lung disease as follows:
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• Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden. Note: "Greater than lobar" = "in more than 1 lobe".

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Aznar MA, Good CR, Barber-Rotenberg JS, Agarwal S, Wilson W, Watts A, Zhang Z, Gonzales D, Donahue G, Hwang WT, Rennels AK, Rech AJ, Kuramitsu S, Huang H, Glastad KM, Alexander KA, Plesa G, Dowd E, Brennan A, Siegel DL, Tanyi J, Haas A, Torigian DA, Nadolski G, Gonzalez VE, Hexner EO, Fraietta JA, Jadlowsky JK, Young RM, Berger SL, June CH, O'Hara MH. Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer. Cell Rep Med. 2025 Sep 16;6(9):102301. doi: 10.1016/j.xcrm.2025.102301. Epub 2025 Aug 18.

  PMID: 40829595 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Mark O'Hara, MD

  Assistant Professor of Medicine, Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: October 27, 2017
• Study Start: September 15, 2017
• Primary Completion: February 20, 2025
• Study Completion: February 20, 2025
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (1)