Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Eye Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Nivolumab

Ipilimumab

Relatlimab

Liver Extracts

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

3 weekly doses of SD-101 given via hepatic artery infusion over 2 cycles

SD-101 doses will be delivered via hepatic artery infusion using pressure enabled drug delivery using the TriNav device

SD-101

During Cohort B, nivolumab will be administered together with SD-101 and during Cohort C, it will be administered with ipilimumab and SD-101

During Cohort C, ipilimumab will be administered together with nivolumab and SD-101

During optional Cohort C1, nivolumab and relatlimab will be administered with SD-101

Nivolumab and Relatlimab

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.

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.

Sentinel Cohort: Two doses of SD-101 (0.5mg and 2mg) administered 2 weeks apart via PEDD/HAI using the TriNav device.

Cohorts A, B, C, and Phase 1b: Three weekly doses of SD-101 (given over two 52-day cycles) in dose-escalation fashion (2mg, 4mg, 8mg-optional) via PEDD/HAI using the TriNav device.

Cohort D (optional): Two weekly doses of SD-101 (given over two 52-day cycles) via PEDD/HAI using the TriNav device.

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

As a measure of safety, adverse events will be graded according to CTCAE v5.0.

A standard 3+3 dose-escalation design will be employed to determine the MTD or optimal dose.

As a measure of activity, ORR will be assessed. ORR will be assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

As a measure of activity, OS will be assessed. The events for the assessment of 12-month OS are death events.

The choice of single- or dual-agent CPI therapy together with SD-101 for Phase 1b will consider AEs/SAEs per CTCAE v5.0.

The choice of single- or dual-agent CPI therapy together with SD-101 for Phase 1b will consider response rates per RECIST v1.1 from Cohorts B and C in Phase 1.

As a measure of activity, iRECIST will be utilized to determine ORR.

As a measure of activity, mRECIST will be utilized to determine ORR.

As a measure of activity, RECIST 1.1 will be utilized to determine hepatic-specific response rate (HRR).

As a measure of activity, RECIST 1.1 will be utilized to determine duration of response (DOR).

As a measure of activity, RECIST 1.1 will be utilized to determine overall progression-free survival (PFS).

As a measure of activity, RECIST 1.1 will be utilized to determine clinical benefit (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma	NCT04935229	Metastatic Uvea...	SD-101 Nivolumab Ipilimumab Nivolumab and R...	18 Years -	TriSalus Life Sciences, Inc.
Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma	NCT04935229	Metastatic Uvea...	SD-101 Nivolumab Ipilimumab Nivolumab and R...	18 Years -	TriSalus Life Sciences, Inc.

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