# Ph1 Study of T-Vec given endoscopically for advanced pancreatic cancer IN 17248 (11/21/2016)

> **NIH FDA R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $250,000

## Abstract

ABSTRACT
This Orphan Drug Grant application is for a phase 1 clinical trial of talimogene laherparepvec (T-VEC), an
oncolytic virus administered endoscopically, in the treatment of unresectable pancreatic cancer. Advanced
pancreatic cancer is unfortunately nearly universally fatal with an estimated dismal median five-year survival of
6.8% for locally advanced disease and 2.8% for patients presenting with distant metastasis. We propose an
investigator-initiated study in pancreatic cancer of T-VEC, a first in class oncolytic virus approved for the
treatment of melanoma. No therapy prolonging survival more than several months is currently available to
pancreatic cancer patients, and the failure of immunotherapy trials to enhance survival has been attributed to
the unique immunosuppressive tumor micro-environment (TME) in pancreatic cancer. Oncolytic viruses, such
as T-vec, may dramatically alter the TME through release of danger signals and activation of innate immune
pathways.
The proposed study has been approved by the FDA (IND#17248) and was submitted to the Columbia University
IRB on 11/23/2016 (IRB#AAQ9966). T-VEC was previously tested in pancreatic cancer and showed good
tolerability and evidence of activity with two minor responses and one stable disease out of 7 treated patients at
the highest dose tested which was a log lower than the one used in melanoma. This study was abandoned
before the MTD was reached for financial reasons. We now propose to complete this study and dose escalate
to test T-VEC in pancreatic cancer at the same dose routinely used in melanoma.
T-VEC kills tumor cells through direct oncolysis and also through secondary immune activation. Precise
mechanisms of immunogenicity are largely unknown. Pre-clinical models show enhancement in local and
systemic anti-tumor immunity while anecdotal human studies suggest alteration in the TME with increased
CD8+T cell infiltration and decreased numbers of CD4+Foxp3+ regulatory T cells. Precise alteration in the TME
is unknown and it has not been established whether T-VECinduces systemic immunity against cancer antigens.
This study is a collaborative project between Columbia University and Johns Hopkins Medical Institute and the
goals are to (1) define the MTD for T-VEC administered endoscopically in pancreatic cancer, (2) define changes
induced in the local TME by T-VEC, specifically prevalence of T cell subsets, and (3) test whether the vaccine
produces systemic antibody responses against pancreatic tumor antigens and compare these antibody
responses with those that are induced by vaccination with GVAX, a GMCSF secreting irradiated pancreatic
cancer cell line previously shown to alter the TME in pancreatic cancer.
.

## Key facts

- **NIH application ID:** 10001349
- **Project number:** 5R01FD006108-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Yvonne Margaret Saenger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $250,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001349

## Citation

> US National Institutes of Health, RePORTER application 10001349, Ph1 Study of T-Vec given endoscopically for advanced pancreatic cancer IN 17248 (11/21/2016) (5R01FD006108-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001349. Licensed CC0.

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