Cryoablation and Arterial Infusion of SD-101 in Combination With Durvalumab and Tremelimumab

This is a phase I, single site study to determine the safety, tolerability, and efficacy of cryoablation combined with hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma (HCC). After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).

SD-101 (also called nelitolimod) is a CpG oligodeoxynucleotide (CpG-ODN). More specifically, SD-101 is a bacterial DNA fragment that functions as a toll-like-receptor 9 (TLR9) agonist on myeloid-derived suppressor cells (MDSC), plasmacytoid dendritic cells (pDC), and other immune cells. TLR9 activation by SD-101 reprograms the tumor microenvironment (TME) and activates the immune system, rendering the tumor more susceptible to cancer immunotherapies, such as immune checkpoint inhibitors (ICI).

This study will administer SD-101 by pressure-enabled drug delivery (PEDD) directly into the hepatic artery during the tumor cryoablation procedure. This treatment will be followed by the STRIDE regimen, which consists of the administration of 2 immune checkpoint inhibitors: single dose of the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) antibody tremelimumab at 300 mg and once-monthly dose of the anti-Programmed Death-Ligand 1 (PDL1) antibody durvalumab at 1500 mg.

The hypothesis of this phase I study is that treatment with SD-101 will improve the efficacy of tremelimumab plus durvalumab by stimulating a robust systemic antitumoral immune response.

Patients with advanced HCC eligible for ICI treatment will be enrolled. Seven to ten days before the first ICI dose, participants will undergo ultrasound- and/or CT-guided cryoablation of part of a single hepatic lesion and concurrent administration of SD-101. US-guided liver biopsy will also be performed immediately prior to cryoablation as well as 30 days (plus or minus 7 days) afterwards. Participants will continue on ICI therapy infusions per the STRIDE regimen and tumor response will be evaluated by contrast-enhanced multiphase MRI or CT every 8 weeks (plus or minus 7 days) for 1 year. After the first year, tumor assessment will be conducted every 12 weeks (plus or minus 14 days).