TriSalus Life Sciences Presents Phase 1b PERIO-02 Trial Results on Nelitolimod Delivery for Liver Cancers at ASCO 2024

TriSalus Life Sciences, Inc. (Nasdaq: TLSI), a company specializing in oncology, has recently showcased promising data from its Phase 1b PERIO-02 clinical trial at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting. The meeting took place from May 31 to June 4, 2024, in Chicago, Illinois.

The PERIO-02 trial focuses on the hepatic arterial infusion (HAI) of nelitolimod, used in conjunction with TriSalus’s proprietary Pressure Enabled Drug Delivery™ (PEDD™) technology. The study targets adults with Hepatocellular Carcinoma (HCC) or Intrahepatic Cholangiocarcinoma (ICC) and combines HAI with intravenous checkpoint inhibitors.

The PEDD technology aims to overcome the limitations posed by the tumor microenvironment (TME). By modulating pressure and flow, PEDD enhances intravascular therapeutic delivery, improving local drug concentrations in tumors. This method addresses the challenges of delivering therapeutics via intravenous infusions or needle injections, reaching immune cells throughout and around the TME.

Mary Szela, CEO and President of TriSalus, emphasized the potential of the PEDD method, stating, "The findings from the PERIO-02 clinical trial demonstrate the potential of the PEDD method to treat patients with HCC and ICC and provide initial clinical validation that HAI of nelitolimod is well tolerated with encouraging immunologic activity."

Key findings from the study included notable responses at the 4 mg dose level in cohort C. All three patients in this cohort achieved disease control, with one patient experiencing a complete response (CR) in the liver, another observing a partial response (PR) with a 31% reduction, and the third maintaining stable disease (SD). Specifically, patient 101-017 showed reductions in liver lesions and stability in extra-hepatic lymph nodes over time, with significant improvements observed as early as day 53 and continuing through day 154.

Median progression-free survival (PFS) for this cohort exceeded 120 days, and median overall survival (OS) had not been reached, ranging between 120 and 170 days. Immune effects of nelitolimod included increases in liver tumor CD4 and CD8 T cells, as well as an improved CD8 T cell to myeloid-derived suppressor cell (MDSC) ratio. Gene expression changes indicated enhanced Th1 programming and increased levels of granzyme A, IFNγ, and CXCL10 in both liver tumors and surrounding normal liver tissues. Plasma marker levels also showed beneficial shifts, with increased IL-2R and CXCL10 expression and decreased IL-17A, IDO, and NT5E (CD73).

Dr. Steven C. Katz, Chief Medical Officer at TriSalus, highlighted the implications of these findings, stating, "The effects noted in PERIO-02 patients, including liver myeloid derived suppressor cell depletion and broad tumor microenvironment immune stimulation, are consistent with previously reported data in metastatic liver tumors and locally advanced pancreatic adenocarcinoma."

The PERIO-02 trial is an open-label phase 1 study of nelitolimod administered via the PEDD method. It encompasses dose-escalation cohorts, including nelitolimod alone (Cohort A), with intravenous pembrolizumab (Cohort B), or with intravenous nivolumab plus ipilimumab (Cohort C). Nelitolimod is delivered over two cycles, with three weekly doses per cycle. Comprehensive correlative studies are conducted using blood, liver tumor, and normal liver biopsies.

The PERIO-02 trial represents a significant step forward in addressing the immunosuppressive environment created by many tumors, which often renders current immunotherapies ineffective in the liver and pancreas. The results support the hypothesis that nelitolimod delivered via PEDD may have favorable immune effects both within the liver and systemically.

TriSalus Life Sciences remains committed to advancing innovative treatments for patients with liver and pancreatic tumors, partnering with leading cancer centers, and leveraging its deep expertise in immuno-oncology.