Targeted Intra-arterial Gemcitabine vs. Continuation of IV Gemcitabine Plus Nab-paclitaxel Following Induction with Sequential IV Gemcitabine Plus Nab-paclitaxel and Radiotherapy for Unresectable Locally Advanced Pancreatic Cancer (TIGeR-PaC): A Randomized Phase 3 Multicenter Study Presented at the 2023 ASCO Gastrointestinal (ASCO GI) Cancers Symposium

Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following induction with sequential IV gemcitabine plus nab-paclitaxel

and radiotherapy for unresectable locally advanced pancreatic cancer (TIGeR-PaC): A randomized phase 3 multicenter study

Michael J. Pishvaian1,17, Amer H. Zureikat2, Charles D. Lopez3, Kenneth Meredith4, Emmanuel E. Zervos5, Hassan Hatoum6, Ki Y. Chung7, Daniel J. Berg8, Antonio Ucar9, Ripal T. Gandhi9, Reza Nazemzadeh10, Nainesh Parikh11, Paula M. Novelli2, Brian Kouri12, Christopher Laing13, Brian A. Boone14, Thor Johnson15, Susan E. Bates16, Ramtin Agah17, Karyn A. Goodman18

1Johns Hopkins University, Washington, DC; 2University of Pittsburgh Medical Center, Pittsburgh, PA; 3Oregon Health & Science University, Portland, OR; 4Sarasota Memorial Health Care System, Sarasota, FL; 5East Carolina University, Greenville, NC; 6University of Oklahoma, Oklahoma City, OK; 7Prisma Health Cancer Institute, Boiling Springs, SC; 8University of Iowa, Iowa City, IA; 9Miami Cancer Institute, Miami, FL; 10Levine Cancer Institute, Charlotte, NC; 11Moffit Cancer Center, Tampa, FL; 12Wake Forest Baptist Medical Center, Winston-Salem, NC; 13Sutter Cancer Center, Sacramento, CA; 14West Virginia University, Morgantown, WV; 15Medical University of South Carolina, Charleston, SC; 16Columbia University, New York, NY; 17RenovoRx, Los Altos, CA; 18Mount Sinai Health System, New York, NY

BACKGROUND

Prognosis for locally advanced pancreatic cancer (LAPC) remains dismal despite advances in cancer therapy.

Local disease control is important in these patients beyond systemic therapies:

• Localized dual-balloon-mediated delivery of intra-arterial gemcitabine (IAG) was demonstrated to be safe in this patient population1

TIGeR-PaC is an ongoing phase III clinical trial (NCT03257033i) comparing the efficacy of IAG to the standard-of-care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC.

Measuring survival outcome as the primary endpoint, TIGeR-PaC is composed of 3 phases:

• Induction phase
• Randomized treatment
• Continuation therapy

DESIGN

SCREEN

• LAPC diagnosed within 6 weeks
• ECOG 0-1

INDUCTION

• 3 cycles of GN
• 1 cycle of radiation (per site preference)

•	IMRT	50 Gy in 25 fractions with concurrent capecitabine, or
•	SBRT	33 Gy in 5 fractions

RANDOMIZED TREATMENT

Patients without progressive disease (PD) receive:

• IAG (8 bi-weekly treatments), or
• GN (4 cycles)

CONTINUATION THERAPY

Per investigator's preference, patients without PD receive:

• GN (until PD), or
• Capecitabine (until PD)

SURVIVAL

OVERVIEW

The phase III clinical trial, TIGeR- PaCi, is investigating the benefits of IAG compared to SoC IVG in LAPC patients

INDUCTION					RANDOMIZED
IV Gemcitabine +					IV Gemcitabine
Nab-paclitaxel				control	+ Nab-paclitaxel
2 months					4 months
Radiation					1:1	Continuation Therapy
RANDOMIZE
SBRT	until progression
					Intra-arterial
IV Gemcitabine +				test	Gemcitabine
Nab-paclitaxel					8 bi-weekly tx
1 month					4 months

• Decision to remove IMRT radiation due to observed differences in toxicity vs. SBRT

1Rosemurgy AS, Ross SB, Vitulli PL, Malek R, Li J, Agah R. Safety Study of Targeted and Localized Intra-Arterial Delivery of Gemcitabine in Patients with Locally Advanced Pancreatic Adenocarcinoma. J Pancreat Cancer. 2017;3(1):58-65.

Published 2017 Aug 1. PMID: 30631844

UPDATE/CURRENT

ENROLLMENT

As of September 1, 2022:

• 189 patients enrolled

INDUCTION DROPOUT

Expected	22%	23%
35%		Restricted mode of
	Progression	(S)AE in	17% IMRT
	Radiation	radiation to SBRT only
	55%
Observed	Other		6% SBRT	Current Dropout
53%			38%

We modified the protocol December 2021 to address disproportional, radiation-associated induction dropout rates in patients receiving IMRT. Following this amendment, our current dropout rate decreased from 53% to 38%.

RANDOMIZATION

As of December 21, 2022:

• 47 patients randomized following induction with SBRT only

SAFETY

There was no difference in adverse event, serious (SAE) or not, between the 2 arms (20% in each), with the most common SAE being gastrointestinal related for both arms.

FUTURE

INTERIM ANALYSIS

Planned at 26 events. As of December 21, 2022, TIGeR-PaC has:

• 25 events

Patients with PD at any point post-randomization are followed for survival only	iClinicalTrials.gov
• 1° endpoint is overall survival; 80% power to detect a hazard ratio of 0.6 between both arms