# Total Neoadjuvant Therapy (TNT) for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

> **NIH NIH P50** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $645,670

## Abstract

PROJECT SUMMARY/ABSTRACT – RP1
Surgery is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC) but
is available to only <20% of patients. For the 20%-30% of patients with borderline resectable or locally advanced
(BR/LA; involving major abdominal vasculature) PDAC, neoadjuvant therapy with induction chemotherapy, with
or without radiotherapy, is the emerging standard. This sequence with chemotherapy up-front provides the
opportunity to downstage tumors to allow curative resection. Importantly, early treatment of micrometastatic
disease helps select patients who are likely to benefit from surgery and spares unnecessary surgery in those
who would not benefit.
Evidence to date supports neoadjuvant therapy, but a more-structured, comprehensive approach is needed,
which requires rigorous prospective evaluation. Moreover, there are currently no biomarkers that reliably predict
treatment response or resistance. This knowledge is essential to appropriately select patients who will benefit
from specific treatment regimens and to modulate treatment for individual patients.
We will evaluate the efficacy of total neoadjuvant therapy (TNT) combining novel triplet chemotherapy with
ablative-dose radiotherapy (AD-XRT), given before surgery, in a phase II trial (Aim 1). This trial will assess the
promising 5-fluorouracil/leucovorin + liposomal-irinotecan + oxaliplatin (NALIRIFOX) regimen, administered
entirely up-front for 4 months, followed by AD-XRT (biological equivalent dose of 100 Gy, delivered in 15-25
fractions, with capecitabine as radiosensitizer). The primary endpoint is event-free survival, with events defined
as progression, recurrence after surgery, or death.
Toward the development of biomarkers of treatment response after TNT, we will assess the potential of (Aim
2A) radiomics analysis of CT images and (Aim 2B) functional FDG-PET and novel immunoPET using 89Zr-
HuMab-5B1 that recognizes cancer antigen 19-9 (CA19-9) to monitor treatment response, assess surgical
resectability, and predict survival. Using blood samples collected on the trial, we will also evaluate circulating
tumor DNA (measured by MSK-ACCESS targeted sequencing) and serum CA19-9 for the same purpose (Aim
3).
This clinical trial aims to define TNT as a new treatment standard for BR/LA PDAC. The planned correlative
studies promise to identify noninvasive biomarkers of response after TNT that may be rapidly translated to the
clinic to allow adaptive disease management. As patients with BR/LA PDAC stand to benefit greatly from
improvements in treatment and monitoring, because of the opportunity to enable curative resection, this project
will likely have a major impact on outcomes in PDAC overall.

## Key facts

- **NIH application ID:** 10333515
- **Project number:** 1P50CA257881-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alice Chia- chi Wei
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $645,670
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333515

## Citation

> US National Institutes of Health, RePORTER application 10333515, Total Neoadjuvant Therapy (TNT) for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma (1P50CA257881-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10333515. Licensed CC0.

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