# Phase I - II Study of Ad/PNP(IND14271,1/19/10)for HNSCC(OrphanDrugDes,14-4438,6/8/15)

> **NIH FDA R01** · EMORY UNIVERSITY · 2020 · $500,000

## Abstract

Abstract
Over the past 15 years, our laboratories have pursued a mechanism for solid tumor sensitization using the E.
coli PNP gene. The approach involves gene transfer with an adenoviral construct, Ad/PNP, and Gene Directed
Enzyme Prodrug Treatment or GDEPT. Unique aspects of the strategy include intratumoral generation of
fluoroadenine, a purine base that markedly disrupts the non-cycling tumor cell compartment, including tumor
progenitor cells. We believe the robust destruction of tumor parenchyma in this manner may also favorably
impact checkpoint blockade and immunologic tumor cell clearance. The basic work underlying the strategy has
been funded previously by approximately $10 million in NCI support. Preclinical safety and efficacy have been
confirmed by many laboratories worldwide, and the strategy is supported by an extensive preclinical database.
Our group has obtained an IND and conducted the first clinical trial of the approach in end-stage head and neck
squamous cell carcinoma (HNSCC), with directed intratumoral inoculation to deliver Ad/PNP. The study
focused on individuals with no other therapeutic options, and received orphan drug designation from FDA
(Approval #14-4438). Our Phase 1 trial was completed and published in late 2015, included 12 patients, and
demonstrated excellent safety and efficacy. In our end-of-phase-1 meeting with FDA, we discussed the serious
unmet clinical need in the setting of end-stage head and neck cancer, the poor response to conventional
therapy, and evidence of strong anti-tumor activity using Ad/PNP. We were informed that the FDA would be
willing to discuss BLA based on an endpoint of overall response rate, if we can show significant improvement
over standard of care. Our Phase 1 data indicates significant improvement over all standard therapeutic
modalities in this setting. The purpose of the current application is to conduct a Phase 1/2 trial at Stanford
University of repeat administration using Ad/PNP followed by systemic fludarabine, as a way to gain additional
information prior to expansion towards a larger patient trial. Through this RO1, we will treat 10 patients, and
incorporate a number of new mechanistic and biometric endpoints carried out by experienced laboratories at
Emory University. IND approval and orphan drug status for the approach are in place, and GMP-grade
adenovirus is available for the study. The work will furnish a means to advance a novel and very potent
anticancer agent (fluoroadenine) that confers durable tumor regression.

## Key facts

- **NIH application ID:** 9727786
- **Project number:** 5R01FD005746-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** EBEN L. ROSENTHAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $500,000
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9727786

## Citation

> US National Institutes of Health, RePORTER application 9727786, Phase I - II Study of Ad/PNP(IND14271,1/19/10)for HNSCC(OrphanDrugDes,14-4438,6/8/15) (5R01FD005746-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9727786. Licensed CC0.

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