Hepatic Arterial Infusion of the Class C TLR9 Agonist SD-101 in Pressure Enabled Regional Immuno-Oncology (PERIO) Phase 1 Trials for Liver Tumors

Monday, March 6, 2023

4:12 PM – 4:21 PM

Location: Phoenix Convention Center, 225AB

Presenting Author(s)

RS

Rahul Sheth, MD

Associate Professor
MD Anderson

Disclosure(s): Boston Scientific: Consultant (), Research Grant or Support (); Medtronic: Consultant (); Replimune: Consultant (Ongoing); Siemens: Consultant (Ongoing); Trisalus: Consultant ()

Author/Co-author(s)

Joshua Kuban, MD

Associate Professor
University of Texas MD Anderson Cancer Center
Joshua Weintraub, MD, FSIR, FACR (he/him/his)

Professor of Radiology (in Surgery)
New York Presbyterian Hospital - Columbia University Irving Medical Center
EW

Eric Wehrenberg-Klee, MD

Faculty
Massachusetts General Hospital
PN

Paula Novelli, MD FSIR

Associate Professor of Radiology
University of Pittsburgh Medical Center
Carin Gonsalves, MD

researcher
Jefferson University
Robert D. Adamo, MD

Assistant Professor
Thomas Jefferson University Hospital
AK

Alex Kim, MD

researcher
National Vascular Physicians
SP

Sapna Patel, MD

researcher
MD Anderson Cancer Center
MJ

Milind Javle, MD

researcher
MD Anderson Cancer Center
SL

Sunyoung Lee, MD

researcher
MD Anderson Cancer Center
RC

Richard Carvajal, MD

researcher
Columbia University
MO

Marlana Orloff, MD

researcher
Jefferson University
KM

Kamaneh Montazeri, MD

Instructor in Medicine, Harvard Medical School
Massachusetts General Hospital
DD

Diwakar Davar, MD

researcher
University of Pittsburgh Medical Center
DG

David Geller, MD

researcher
University of Pittsburgh Medical Center
ZN

Zoe Nguyen, n/a

researcher
Trisalus Life Sciences
AH

Ann-Marie Hulstine, n/a

researcher
Trisalus Life Sciences
BC

Bryan Cox, PhD.

Chief of Research
TriSalus Life Sciences
SK

Steven Katz, M.D.

Chief Medical Officer
TriSalus Life Sciences

Disclosure(s):

Rahul Sheth, MD: Boston Scientific: Consultant (), Research Grant or Support (); Medtronic: Consultant (); Replimune: Consultant (Ongoing); Siemens: Consultant (Ongoing); Trisalus: Consultant ()

Joshua Kuban, MD: Argon Medical: Advisory Committee or Review Panel Member (Ongoing), Consultant (Ongoing); Bayou Surgical: Ownership Interest (Ongoing); Boston Scientific: Advisory Committee or Review Panel Member (Ongoing), Board Membership (Ongoing), Consultant (Ongoing), Speaking and Teaching (Ongoing); Elekta: Contracted Research (Ongoing); Ethicon J&J: Advisory Committee or Review Panel Member (Ongoing), Consultant (Ongoing), Speaking and Teaching (Ongoing); Lunglife AI: Board Membership (Ongoing), Contracted Research (Ongoing); Pfizer Inc: Contracted Research (Ongoing); SIRTex: Consultant (Ongoing), Independent Contractor (Ongoing), Speaking and Teaching (Ongoing); Trisalus Life Sciences: Consultant (Ongoing), Contracted Research (Ongoing)

Joshua Weintraub, MD, FSIR, FACR: Instylla, Inc.: Advisory Committee or Review Panel Member (Ongoing)

Paula Novelli, MD FSIR: No financial relationships to disclose

Purpose: Patients with primary and metastatic liver tumors experience limited benefit with immune checkpoint inhibitor (ICI) monotherapy in part due to a highly immunosuppressive tumor-microenvironment (TME) and in part due to high hepatic pressures. Hepatic arterial infusion (HAI) of the class C toll-like receptor-9 agonist (TLR-9A) SD-101 using the TriNav Pressure-Enabled Drug Delivery (PEDD) device has the potential to enhance TME sculpting through improved intrahepatic delivery and minimization of systemic exposure to the drug. This approach may overcome limitations in the use of TLR-9A associated with direct needle injection or systemic delivery.

Materials and Methods: PERIO-01 and PERIO-02 are open-label first-in-human Phase 1b trials of SD-101 given by HAI using PEDD in uveal melanoma with liver metastases (UMLM), advanced hepatocellular carcinoma (HCC), and advanced intrahepatic cholangiocarcinoma (ICC) (NCT04935229 and NCT05220722). The studies consist of dose-escalation cohorts of single agent SD-101 alone and with ICI. SD-101 is delivered over 2 cycles via HAI using TriNav and standard intra-arterial access, with 3 weekly doses per cycle. Procedural data for the first 12 months of the PERIO program was collected and analyzed. Enrollment in these studies is ongoing.

Results: Over the first 12 months of the PERIO program 23 participants were treated at 5 clinical trial sites, and 87 infusions were completed. 74% of participants were treated via sectoral approach; 22% via segmental approach; and 4% via a whole liver approach (single infusion location). 92% of procedures required a single TriNav device to infuse to all target locations. The average infusion time was 40 minutes. There were no procedure-related serious adverse events reported, with 15 procedure-related adverse events. Minor adverse events included puncture site pain, bruising, or hematoma. Thirteen immune-related adverse events were reported, including fever and chills. There were no severe (Grade 3 or higher) immune-related events, specifically cytokine release syndrome, in the procedure rooms or during follow-up.

Conclusion: These are the first clinical trials to study HAI of a TLR-9A with PEDD and suggest safety, tolerability and feasibility of this approach in the multicenter setting.