SD-101 and Checkpoint Blockade Shows Early Favorable Outcomes in UMLM

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SD-101 delivered via pressure-enabled drug delivery (PEDD) with the TriNav® Infusion System is well-tolerated and associated with immunologic effects in within the liver and systemically when given in combination with intravenous checkpoint inhibitors for the treatment of patients with metastatic uveal melanoma with liver metastases (UMLM), according to phase 1 data from the PERIO-01 study (NCT04935229).¹

Findings presented during the late-breaking oral presentation session at the Society of Immunotherapy for Cancer (SITC) 2023 Annual Meeting showed that the median progression-free survival (PFS) was 11.7 months and the disease control rate (DCR) was 81% among the 7 patients with UMLM treated with the optimal biologic dose of SD-101 at 2 mg in combination with nivolumab (Opdivo).

The overall serious grade 3/4 adverse event (AE) rate related to treatment was 11% (n = 56). No grade 3/4 AEs were seen at the optimal SD-101 dose level plus nivolumab (n = 7). Gastrointestinal (41%), fatigue (30%), and skin toxicity (27%) were the most common AEs, and most were minor. These data are consistent with earlier data of SD-101 from a pancreatic adenocarcinoma trial.

“The results of PERIO-01 highlight the importance of getting the biology right and not just pushing a drug to its maximum tolerated dose. The biological effects of SD-101 are best at the lowest dose tested, revealing tumor microenvironment reprogramming and inflammatory cell trafficking from normal to metastatic liver tumors,” said Sapna Patel, MD, director of the uveal melanoma program at The University of Texas MD Anderson Cancer Center, in a press release.¹ “This is not seen at higher doses of SD-101, and these findings ensure we are entering the next phase with the optimal dose in combination with checkpoint inhibition, for patients with metastatic uveal melanoma.”

About PERIO-01

The phase 1 PERIO-01 study is an open-label, first-in-human trial of SD-101 for the treatment of patients with UMLM.² Treatment with SD-101 is administered by hepatic arterial infusion with TriNav using PEDD, and the study consists of dose-escalation cohorts which are evaluating SD-101 at 2, 4, or 8 mg alone or combined with immune checkpoint inhibition.

A total of 56 patients were enrolled at the data cutoff date of September 29, 2023, and had received at least 1 dose of SD-101.¹ Sixteen patients (29%) included in the study were treatment-naïve, and 40 (71%) had failed at least 1 previous line of therapy. These patients included 8 (14%) who were on their third or greater line of treatment.

Additional findings from the PERIO-01 study showed encouraging early efficacy signals among patients with UMLM. The ctDNA molecular response rate was 65% using specified time points (n=20), and when analyzing the best on-treatment response, the rate was 82% (n = 26). Clearance of ctDNA was noted in 59% of subjects when assessing the best on-treatment response.

Among all patients, there were 2 partial responses (≥30% decrease) and 5 minor responses (10%-29% decrease) documented as the best on-treatment response. Of those treated with SD-101 via PEDD plus intravenous nivolumab, increases in CD8+ T cells, CD4+ T cells, and natural killer (NK) cells were observed within patients’ liver metastases. SD-101 at a dose of 2 mg in combination with nivolumab also led to decreases in monocytic myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells in liver metastases. Additionally, encouraging peripheral immune signals were observed, as well as increases in IFNγ, soluble IL2-receptor, IL-15, IL-18, T cell activation, and NK cell proliferation which were found in the blood.

“We are encouraged to see that SD-101 is well tolerated when given by PEDD, in association with immunologic effects within the liver and systemically, which may enable better outcomes with systemic checkpoint inhibition,” said Steven C. Katz, MD, FACS, chief medical officer at TriSalus, in a press release.¹ “The PFS and ctDNA molecular response data in PERIO-01 patients in combination with nivolumab are promising for UMLM and as well as for other indications that we are pursuing.”

PERIO Trials

SD-101, an investigational class C toll-like receptor-9 agonist, is being evaluated in the Pressure-Enabled Regional Immuno-Oncology (PERIO) clinical trials. Treatment with SD-101 is being administered to patients intravascularly in 3 phase 1 trials.

In addition to PERIO-01, the phase 1 trial for patients with UMLM, the PERIO-02 trial is assessing whether this same platform approach used in PERIO-01 of SD-101 and PEDD can improve the performance of systemic checkpoint inhibitors in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma (NCT05220722).

Additionally, PERIO-03 is an open-label, phase 1/1b study (NCT05607953) is evaluating a pressure-enabled intrapancreatic infusion of SD-101 as a monotherapy or in combination with intravenous checkpoint blockade in adults with locally advanced pancreatic cancer.

REFERENCES:

1. Late-breaking phase 1 liver metastasis data from TriSalus presented at SITC 2023 supports development of innovative immuno-oncology approach for liver and pancreas indications. News release. TriSalus Life Sciences Inc. November 4, 2023. Accessed November 6, 2023. https://tinyurl.com/mucs5jfd

2. Intrahepatic delivery of SD-101 by pressure-enabled regional immuno-oncology (PERIO), with checkpoint blockade in adults with metastatic uveal melanoma. ClinicalTrials.gov. Updated January 31, 2023. Accessed November 6, 2023. https://clinicaltrials.gov/study/NCT04935229