TriSalus Life Sciences & Roger Williams Medical Center Announce Initiation of Phase 1 Clinical Trial for a Novel Delivery Technology

TriSalus Life Sciences recently announced the initiation of a new clinical trial assessing the safety and feasibility of an innovative new treatment that combines its intravascular, tumor-directed proprietary Pressure-Enabled Drug Delivery (PEDD) approach with standard of care systemic chemotherapy.

The goal of this clinical trial is to perform targeted delivery of the most toxic components of standard-of-care treatment regimen deep into pancreatic tumors using a novel approach that accesses the tumor via pancreatic veins. The chemotherapy involved is for the treatment of adults diagnosed with unresectable, pancreatic carcinoma. With the number of newly diagnosed patients with pancreatic cancer rising and fewer than 20% suitable for surgery(1), improved treatment options for pancreatic cancer are a critical health care need.

Traditional approaches for targeted therapeutic delivery to the pancreas rely on the use of the arterial system. The pancreatic arterial supply, however, poses unique anatomic challenges as the terminal pancreatic arteries are not large enough to accommodate delivery devices. This limits the ability for highly focused delivery of therapeutics to pancreatic tumors. TriSalus has developed a new retrograde venous proprietary approach using the simpler pancreatic venous system, making it far more suitable for PEDD.

The presence of highly dense tissue architecture and abnormal poor blood flow into solid tumors are critical barriers to drug delivery, resulting in less than 1% of systemic drug administration delivered into tumors with conventional therapies.(2)

PEDD with SmartValve technology is a self-expanding, one-way micro-valve that enables optimal infusion pressures for deeper therapeutic penetration. Treatment is delivered directly into solid tumors with the goal to avoid healthy tissue while optimizing therapeutic effect. This pressurized delivery has the potential to open collapsed vessels in tumors and helps promote therapy delivery.

This study is designed to assess the technical success and safety of administering oxaliplatin through retrograde venous infusion (RVI) followed by systemic administration of FOLFIRI, a regimen containing folinic acid, fluorouracil, and irinotecan. Secondary measures of the study include local progression free survival, systemic progression free survival, overall survival, radiographic response rates, serologic response rates, and neurotoxicity from oxaliplatin. Exploratory measures include correlation of infusion pressures with treatment response, in addition to serum oxaliplatin pharmacokinetics following PEDD-RVI. Patients, who are new to treatment and have received first-line systemic therapy, are eligible for this trial.

“We’ve made significant advances in developing therapeutics to address various forms of cancer, but solid tumors of the pancreas have significant barriers that prevent therapies from penetrating the entire tumor. This trial will help us evaluate the role of this novel drug delivery technology in overcoming tumor infusion barriers and delivering the most toxic component of the regimen deep into the solid tumor,” said Ritesh Rathore, MD, of Roger Williams Medical Center in Providence, RI, and Principal Investigator for the trial.

“We hope this trial not only results in improved outcomes with standard of care chemotherapy treatments for pancreas cancer, but also enables use of this novel delivery platform for immuno-oncology agents in the future. Our focus on improving the therapeutic index for pancreas tumor treatments through regional delivery solutions designed to overcome high intra-tumoral pressures will hopefully have broad application and address critical unmet medical needs,” said Steven C. Katz, MD, Director of The Office of Therapeutic Development at Roger Williams Medical Center.

“At TriSalus Life Sciences, we have devoted all of our resources to the tri-pronged approach of building intravascular, tumor-directed, organ specific therapeutic regimens that can be safely delivered regionally either independently or in combination with standard of care to improve the lives of patients,” said Mary T. Szela, President and CEO of TriSalus. “We’re pleased to partner with Roger Williams Medical Center for this study, and we are grateful to the patients and families who participate in this study.”

The open-label trial will be conducted at Roger Williams Medical Center as a single-arm, dose-escalation Phase 1 study of patients with unresectable pancreatic adenocarcinoma. The trial will enroll 9 patients, and if dose-limiting toxicities (DLT) are not encountered, a total of 18 patients will be enrolled. For more information, visit www.clinicaltrials.gov or www.newpancancertrial.com; or contact Ashley Moody, BSN, RN, Immunotherapy Research Nurse Manager, 401-456-2268 or email at alarkin@chartercare.org.

Pancreatic cancer is the third leading cause of cancer deaths in the United States (US), responsible for an estimated 45,750 deaths in 2019, with a 5-year survival rate of approximately 9%.(3) The dismal prognosis of pancreatic cancer can be attributed to several factors: initial diagnosis at an advanced stage, aggressive nature of the disease, resistance to conventional treatment options of chemotherapy and radiation therapy, the presence of multiple genetic/epigenetic alterations and complex tumor microenvironments. Surgical resection of the primary tumor with negative margins is still the cornerstone of potentially curable therapy, but only 15-20% of patients are eligible at diagnosis.

The proprietary Pressure-Enabled Drug Delivery (PEDD) approach with SmartValve technology is FDA 510(k) cleared and features a self-expanding, nonocclusive, one-way valve, which infuses therapeutics into a solid tumor at a pressure higher than the baseline mean. This pressurized delivery opens collapsed vessels in tumors and enables perfusion and therapy delivery into hypoxic areas of solid tumors.

Located in Providence, RI, Roger Williams Medical Center is a 220-bed acute care teaching hospital affiliated with Boston University Medical Center. It is host to the Roger Williams Cancer Center, a nationally recognized leader in cancer treatment and related research, as well as the state’s only Bone Marrow Transplantation Unit, and also offers clinical centers of excellence in digestive diseases, bariatric surgery and behavioral health. Roger Williams is an affiliate of Prospect Medical Holdings, Inc., a health and hospital system of 17 hospitals including a network of more than 162 outpatient facilities and clinics in Southern California, Connecticut, New Jersey, Pennsylvania, and Rhode Island.

TriSalus Life Sciences is dedicated to improving patient outcomes in pancreatic and other highly intractable solid tumors. TriSalus Infusion Systems have the potential to deliver diagnostic, therapeutic agents, and immuno-stimulants directly into tumor vasculature powered by its proprietary Pressure-Enabled Drug Delivery (PEDD) approach with SmartValve technology to improve the distribution and penetration of therapy in solid tumors. This innovative approach has the potential to allow for the administration of multiple mechanisms that can work together to overcome inherent immune suppression within the solid tumor microenvironment. For more information, please visit www.trisaluslifesci.com.

References
1. Griffin, J. F., Poruk, K. E. & Wolfgang, C. L. Pancreatic cancer surgery: past, present, and future. Chin J Cancer Res 27, 332–348 (2015).
2. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nature Reviews Materials 1, 16014 (2016).
3. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2019. CA: A Cancer Journal for Clinicians 69, 7–34 (2019).