On June 12, 2023 TriSalus Life Sciences Inc., (TriSalus or the Company), an oncology company in the process of going public through a business combination transaction (the Business Combination) with MedTech Acquisition Corporation (Nasdaq: MTAC) (MedTech or MTAC), reported additional Phase 1 clinical data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting taking place in Chicago, Illinois, from June 2-6, 2023 (Press release, TriSalus Life Sciences, JUN 12, 2023, View Source [SID1234632669]).
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TriSalus’ ongoing Phase 1 Pressure-Enabled Regional Immuno-Oncology (PERIO-01) (NCT04935229) clinical study for uveal melanoma with liver metastases (UMLM) is studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly by TriSalus’ TriNav Infusion System (TriNav) using the Company’s proprietary Pressure-Enabled Drug Delivery (PEDD) method of administration. PERIO-01 is evaluating whether this platform approach can improve the performance of systemic checkpoint inhibitors in patients with UMLM.
"The data presented by Dr. Kamaneh Montazeri from Mass General Brigham at ASCO (Free ASCO Whitepaper) reflect important clinical progress of our Phase 1 PERIO-01 trial and builds on the promising data released in April," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus. "We are pleased that SD-101 in combination with systemic checkpoint inhibition and delivered with TriNav was well tolerated based on a low treatment related serious adverse event rate of 5% and resulted in immune cell activation and natural killer cell expansion. We look forward to moving into Phase 2 later this year and are optimistic about the potential of SD-101 playing an important role in the management of patients with UMLM."
Pharmacokinetic data indicate that the strategy of delivering a toll-like receptor-9 agonist with the PEDD method results in high drug levels in the liver, while the drug is undetectable after four hours in the serum in 97% of patients with available data. The immune effects in liver metastases and the blood are consistent with broad tumor microenvironment modulation and the ability of SD-101 to deplete myeloid derived suppressor cells (MDSCs) in the liver.
PERIO-01 is an open-label, first-in-human Phase 1 trial of SD-101, administered by hepatic arterial infusion with TriNav using PEDD in UMLM. The study consists of dose-escalation cohorts of SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition. At the data cutoff as of May 12, 2023, 39 patients were enrolled in the PERIO-01 trial, with each having received at least one dose of SD-101. Of the patients with available data, five patients were treatment-naïve and 81% had failed at least one prior line of therapy, including three patients on their sixth-line of treatment.
Following receipt of SD-101, patients demonstrated a statistically significant expansion of peripheral natural killer cells, along with evidence of decreased expression of exhaustion markers on these cells. Increases in serum cytokines, including IFNg and IL-18, also supported systemic immune activation. Additionally, decreased levels of ctDNA levels were observed within eight out of 13 evaluable patients. Stable disease was noted as the best on-treatment response for target lesions in 15 out of 25 patients, with one partial response.
These findings, along with reductions of intratumoral MDSCs and decreases in ARG-1 (arginase 1) and IDO-1 (indoleamine 2,3-dioxygenase-1) gene levels, support the hypothesis that SD-101 delivered via PEDD may have favorable immune effects within the liver and systemically.
Overall, the data emerging from the PERIO-01 trial continues to indicate immunologic changes are occurring within the liver, with decreases in ctDNA and disease control observed across a group of heavily pre-treated patients with UMLM, as well as a low treatment-related serious adverse event rate.
The data were also selected for presentation at the Developmental Therapeutics – Immunotherapy Poster Discussion Session on June 3, 2023 at 3:00pm CT.