nelitolimod (SD-101)

P1, N=10, Recruiting, Northwell Health | Not yet recruiting --> Recruiting

We review and evaluate immune-mediated adverse events from three sets of clinical studies using toll-like receptor 9 (TLR9) agonists (CpG-ODN) as vaccine adjuvants and therapeutic agents in patients with cancer: 1) a comparison of immune-mediated adverse events across phase 1-3 clinical trials of the hepatitis B vaccine HEPLISAV-B (HepB-CpG) with the alum-adjuvanted hepatitis B vaccine (HepB-alum); 2) an analysis of the rates of immune-mediated adverse events across clinical trials of COVID-19 vaccines using the CpG 1018 adjuvant; and 3) the rates of immune-mediated conditions in a study of the CpG-ODN nelitolimod (SD-101) combined with the immune checkpoint inhibitor pembrolizumab in patients with advanced melanoma or head and neck cancer, compared with rates in historical studies of pembrolizumab monotherapy. Data evaluated in this review show no increased risk for potential autoimmune disorders with HepB-CpG or CpG 1018-adjuvanted COVID-19 vaccines. Combining CpG-ODN with a checkpoint inhibitor did not increase the rate of immune-mediated conditions.

Here, we developed a novel whole-cell vaccine, termed MDLSD, by combining mitoxantrone (MTX)-induced ICD with the TLR9 agonist SD-101. Furthermore, mice cured by MDLSD developed long-term immunological memory, characterized by a recall response dominated by IFN-γ+ CD8+ and TNF-α+ T cells, enabling rejection of secondary tumor challenges. Collectively, our findings illustrate that the MDLSD vaccine synergizes the antigenic breadth of ICD with potent TLR9 stimulation to elicit robust DC activation, polyfunctional T-cell responses, and durable immunological memory, offering a compelling strategy for cancer immunotherapy.

P1/2, N=23, Terminated, TriSalus Life Sciences, Inc. | N=89 --> 23 | Active, not recruiting --> Terminated; The decision was made to terminate the study after the completion of Phase 1b enrollment and not proceed with Phase 2. Trial termination was not due to patient safety or data concerns.

P1, N=67, Terminated, TriSalus Life Sciences, Inc. | Active, not recruiting --> Terminated; The decision was made to terminate the study after the completion of Phase 1 enrollment and not proceed with Phase 2. Trial termination was not due to patient safety or data concerns.

Transgenic pigs (oncopigs) with liver tumors received intra-arterial infusions of fluorescently labeled ODN2395 or nelitolimod either via PEDD with a specialized infusion device or with conventional microcatheter delivery in both lobar and selective infusions. PEDD of nelitolimod significantly reduced immunosuppressive MDSCs and an increase in cytotoxic CD8 + T cells within the LM. In conclusion, use of PEDD enhanced targeted therapeutic delivery in swine liver tumors and reduced tumor progression by promoting anti-tumor immunity in murine LM in association with suppressive myeloid cell elimination.

P1, N=10, Not yet recruiting, Northwell Health

P1, N=60, Active, not recruiting, TriSalus Life Sciences, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Oct 2024 --> Sep 2027

P1, N=20, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting

P2, N=23, Active, not recruiting, David Oh | Trial completion date: Oct 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025

P1, N=20, Not yet recruiting, University of California, San Diego

The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery.