NCT04935229

Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma

A Phase 1/1b, Open-Label Study of the Pressure-Enabled Hepatic Artery Infusion of SD-101, a TLR9 Agonist, Alone or in Combination With Intravenous Checkpoint Blockade in Adults With Metastatic Uveal Melanoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: TriSalus Life Sciences, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is an open-label, phase 1/1b study of the pressure-enabled hepatic artery infusion of SD-101, a TLR 9 agonist, alone or in combination with intravenous checkpoint blockade in adults with metastatic uveal melanoma.

Detailed description

In the Sentinel Cohort, patients will receive 2 SD-101 infusions (2 weeks apart) with assessments for toxicity prior to escalating from the first dose level (0.5 mg) to the second dose level (2 mg). In the absence of dose-limiting toxicities (DLTs), each patient will be eligible to transition into Cohort A. In Cohorts A-C and Phase 1b, patients will receive 2 cycles of SD-101. Each cycle consists of 3 consecutive weekly infusions. Escalating doses of SD-101 will be administered alone (Cohort A), together with nivolumab (Cohort B), together with combined ipilimumab and nivolumab (Cohort C), or together with nivolumab and relatlimab (Cohort C1 - optional). Cohorts B and C will begin dosing at the minimum anticipated biological effect level (MABEL(2mg SD-101)). An optional Cohort D may be opened to explore the combination of one or more of the following three CPI regimens with a modified SD-101 dosing schedule with only 2 weekly SD-101 infusions per cycle for 2 cycles: 1. Single-agent nivolumab IV at 480mg every 4 weeks; 2. IV ipilimumab 3mg/kg and IV nivolumab 1mg/kg every 3 weeks for 4 doses each followed thereafter by nivolumab 480mg IV every 4 weeks; 3. Nivolumab 480mg and relatlimab 160mg IV every 4 weeks. Following determination of the recommended MTD or optimal dose of SD-101 for PEDD/HAI and which checkpoint inhibitor (CPI) regimen(s) are tolerated, the study will progress to Phase 1b. Patients in Phase 1b will receive the SD-101 dose selected from Phase 1 together with systemic single- or double-agent checkpoint blockade. The choice of single- or double-agent CPI therapy together with SD-101 for Phase 1b will consider safety data in addition to response rates from Cohorts B and C in Phase 1. Patients enrolled into the main study are eligible to enroll into an optional imaging sub-study investigating the use of 89Zr-Df-crefmirlimab, a biologic PET radioligand for detecting CD8+ T cell lymphocytes. 89Zr-Df-crefmirlimab will be administered by IV at screening and again prior to C2D1 procedures. A PET scan is conducted within 72 hours following the tracer infusion.

Conditions

• Metastatic Uveal Melanoma in the Liver

Interventions

Type	Name	Description
DRUG	SD-101	SD-101 doses will be delivered via hepatic artery infusion using pressure enabled drug delivery using the TriNav device
BIOLOGICAL	Nivolumab	During Cohort B, nivolumab will be administered together with SD-101 and during Cohort C, it will be administered with ipilimumab and SD-101
BIOLOGICAL	Ipilimumab	During Cohort C, ipilimumab will be administered together with nivolumab and SD-101
BIOLOGICAL	Nivolumab and Relatlimab	During optional Cohort C1, nivolumab and relatlimab will be administered with SD-101

Timeline

• Start date: 2021-08-02
• Primary completion: 2024-07-17
• Completion: 2024-07-17
• First posted: 2021-06-22
• Last updated: 2025-10-22

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study