nelitolimod (SD-101) / Dynavax, TriSalus Life Sci, UT MD Anderson Cancer Center - LARVOL DELTA

First-in-human study of neoadjuvant regional delivery of the TLR9 agonist Nelitolimod via pressure enabled drug delivery (PEDD) in resectable microsatellite stable colorectal liver metastases (AACR 2026) - "Abstract is embargoed at this time."

Clinical • First-in-human • P1 data • Oncology

Efficacy and Safety Study to Evaluate SD-101 in Epidermolysis Bullosa (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: Paradigm Therapeutics

New P3 trial

An Open Label Extension Safety Study to Evaluate SD-101 in Epidermolysis Bullosa (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: Paradigm Therapeutics

New P3 trial

INFINITIVE: ImmuNotherapy For PatIeNts wIth colorecTal LIVer MEtastases (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Northwell Health | Not yet recruiting ➔ Recruiting

Enrollment open • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

A narrative review of immune-mediated adverse events in clinical trials of CpG oligonucleotide toll-like receptor 9 agonists. (PubMed, Vaccine) - "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..."

Adverse events • Journal • Review • Head and Neck Cancer • Hepatitis B • Immunology • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor • PD-1

TriSalus Life Sciences Announces Publication Demonstrating Enhanced Delivery and Immune Activation with Nelitolimod Delivered with Pressure-Enabled Drug Delivery in Liver Tumor Models (Businesswire) - "Improved intratumoral delivery: PEDD administration with the TriNav Infusion System resulted in significantly greater distribution of nelitolimod within and around tumors compared with delivery through a conventional microcatheter in an Oncopig model of hepatic tumors; Evidence of enhanced immune activity: Treatment using PEDD was associated with reduced levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) and increased infiltration of cytotoxic CD8+ T cells within the tumor microenvironment...In a murine liver metastasis model, nelitolimod delivered using PEDD significantly reduced tumor growth compared with systemic administration at key time points during the study."

Preclinical • Liver Cancer

Impacts of a Knowledge Mobilization Campaign for Carer-Inclusive Workplace Tools in Canada: Knowledge-to-Action Design Study. (PubMed, JMIR Form Res) - "Phase 1 activities brought in a total of 36,308 views (mean 9077, SD 17,336), 2469 unique views (mean 617, SD 548), 55,445 social media impressions (mean 13,861, SD 19,424), and 432 social media clicks (mean 108, SD 101) across all 4 articles...Results of the campaign suggest that published magazine articles targeted to the respective audiences are the most effective method of knowledge mobilization for this work, recognizing that paid activities had greater reach and better resources for dissemination. Future research in this area should focus on engaging with employers and professional stakeholders more directly."

Journal

Clinical activity of SD-101 with immune checkpoint inhibition (ICI) in metastatic uveal melanoma liver metastasis (MUM-LM) from the PERIO-01 Phase 1 trial (SITC 2023) - P1 | "PFS has been limited, even with approved therapies such as tebentafusp (median 3...Methods PERIO-01 is a phase 1 trial of hepatic arterial SD-101 via PEDD in MUM-LM (NCT04935229), with dose-escalation cohorts as monotherapy (Cohort A), with nivolumab (Cohort B), or nivolumab + ipilimumab (Cohort C)...7 months, MDSC re-programming, and evidence of peripheral and intra-tumoral immune activation. Phase 2 of PERIO-01 is planned for expansion of the optimal dose."

Checkpoint inhibition • Clinical • IO biomarker • Late-breaking abstract • Metastases • P1 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • ARG1 • CD163 • CD4 • CD8 • FASN • IFNG • IL18 • IL2RA • TNFA

Synergistic whole-cell Cancer vaccine combining immunogenic cell death and TLR9 agonist elicits potent prophylactic and therapeutic antitumor immunity. (PubMed, Int Immunopharmacol) - "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."

Journal • Lung Cancer • Oncology • Solid Tumor • CD8 • CD80 • GZMB • IFNG • TNFA

Pneumonitis but not other immune related adverse events (irAEs) associate with pre-treatment immune signatures in early-stage breast cancer patients receiving neoadjuvant immunotherapy (IO): results from 5 IO arms in I-SPY2 (SABCS 2025) - "Methods 356 patients (206 HR+HER2- and 150 TN) across 5 IO arms (69 pembrolizumab (Pembro), 76 Pembro/SD101, 73 durvalumab/olaparib, 62 cemiplimab (Cemi), and 78 Cemi/LAG3) with irAE and pCR data were analyzed. This association was observed exclusively in patients with ImPrint+ tumors, where PD1 mRNA levels predicted pneumonitis. mRNA signatures may help enable early identification and treatment of IO patients likely to develop pneumonitis."

Adverse events • Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • LAG3 • PD-1 • PD-L1

The Impact of Pausing Bruton Tyrosine Kinase Inhibitor Therapy and Responsiveness of Vaccination in Blood Cancer Patients: Primary Outcome Result for the Randomised Improve Trial (ASH 2023) - "At baseline, the geometric mean anti-spike RBD antibody titre was 71.6 U/mL (SD 101.3) in the suspend BTKi group and 132.9 U/mL (SD 82.2) in the continue BTKi group. Between Oct 10, 2022 and June 30, 2023, 99 participants with CLL were randomly assigned to continue BTKi (n=49) or pause BTKi (n=50). Mean age of participants was 70.5 years and 71/99 (72%) were male. 63/99 (64%) were on first line CLL therapy, and 51 (52%) were taking Ibrutinib, with the remaining participants taking Acalabrutinib."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Loss of the OX40 Target in Lymphoma Patients after Combining an Anti-OX40 Agonist Antibody with in Situ Vaccination (ASH 2023) - P1 | "STUDY: Fourteen patients with low-grade lymphoma received low-dose (2Gy x 2) radiotherapy to a single tumor site followed by 5 weekly intratumoral injections of 2 mg CpG-ODN (SD-101, TriSalus Life Sciences) and 3.75 mg anti-OX40 antibody into the same site...This loss was reproduced by in vitro assays where activated blood CD4 T cells exhibited a loss of cell surface OX40 when cultured with BMS-986178... Our observations suggest that treatment with an agonistic anti-OX40 antibody induced a loss of OX40 on the cell surface of effector CD4 T cells in the tumor microenvironment. Fewer molecules of OX40 receptor may have constrained the efficacy of subsequent anti-OX40 infusions and may explain why the clinical responses observed in this study were lower than observed in our past clinical trials of in situ vaccination."

Clinical • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology • Solid Tumor • CD4

Short-term efficacy and safety of intravitreal brolucizumab in diabetic macular edema: A retrospective interventional study. (PubMed, Oman J Ophthalmol) - "The study findings in this cohort demonstrated statistically significant improvement in BCVA and a substantial decrease in SFMT. However, more real-world studies are required to enhance the validation of this study's findings."

Journal • Retrospective data • Cardiovascular • Diabetic Macular Edema • Inflammation • Ophthalmology

PERIO-02: Pressure Enabled Delivery of SD-101 With Checkpoint Blockade for Primary Liver Tumors (clinicaltrials.gov) - P1/2 | N=23 | Terminated | Sponsor: 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.

Checkpoint inhibition • Enrollment change • Trial termination • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • FGFR2

PERIO-01: Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma (clinicaltrials.gov) - P1 | N=67 | Terminated | Sponsor: 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.

Checkpoint inhibition • Trial termination • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine and murine liver tumor models. (PubMed, Front Oncol) - "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."

Journal • Preclinical • Cutaneous Melanoma • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Solid Tumor • CD8 • PTPRC

INFINITIVE: ImmuNotherapy For PatIeNts wIth colorecTal LIVer MEtastases (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Northwell Health

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Advanced Melanoma. (PubMed, Clin Cancer Res) - "In patients with anti-PD-1/PD-L1 treatment-naive advanced melanoma, nelitolimod plus pembrolizumab induced objective responses, including in PD-L1-negative tumors. The treatment combination warrants further study in advanced melanoma."

Clinical • Journal • P2 data • Melanoma • Oncology • Solid Tumor

PERIO-03: Pressure Enabled Intrapancreatic Delivery of SD-101 With Checkpoint Blockade for Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: TriSalus Life Sciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2024 ➔ Sep 2027

Checkpoint inhibition • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Pembrolizumab +/- SD-101 in Hormone-Naïve Oligometastatic Prostate Cancer With RT and iADT (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: David Oh | Active, not recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Mar 2025 | Trial primary completion date: Aug 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Serum immune markers are associated with pathological complete response and immune-related adverse events in immuno-oncology arms of the I-SPY2 breast cancer trial (AACR 2025) - "Patients received paclitaxel with anti-PD-1 (N=49) or anti-PD-1 plus SD-101 (N=65), followed by anthracycline/cyclophosphamide. Serum immune markers may influence tumor immune cell infiltration, potentially affecting the likelihood of achieving pCR and systemic immune activity linked to irAEs. Serum levels of CRP, CXCL10, sCD25, G-CSF, and IFNγ could be used to monitor and predict clinical benefit from anti-PD-1 and immunomodulatory agents. This study also suggests that VEGF-C and granzyme B can be possible candidate prognostic biomarkers for irAEs in patients receiving anti-PD-1 therapy."

Adverse events • Clinical • Immuno-oncology • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CCL2 • CD163 • CRP • CSF3 • CXCL10 • CXCL11 • CXCL13 • CXCL8 • CXCL9 • GZMB • HER-2 • IFNG • IL10 • IL6 • LAG3 • PD-L1 • TNFA • VEGFC

TriSalus Life Sciences Announces $22.0 Million Private Placement… (Businesswire) - "TriSalus Life Sciences, Inc...announces...that it has entered into a securities purchase agreement with certain investors for shares of its common stock to raise approximately $22.0 million in gross proceeds."

Financing • Oncology

TriSalus Life Sciences Reports Q4 and Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Enrollment was completed in the PERIO-03 Phase 1 trial investigating nelitolimod in locally advanced pancreatic cancer. Final data are expected mid-2025, with next steps to be determined based on results."

Enrollment closed • P1 data • Pancreatic Cancer

A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies. (PubMed, Clin Cancer Res) - "Clinical results of T cell costimulatory receptor agonism have now repeatedly been inferior to the motivating preclinical results. Our study highlights potential barriers to clinical translation, particularly differences in preclinical and clinical reagents and the complex biology of these coreceptors in heterogenous T cell subpopulations, some of which may antagonize immunotherapy."

IO biomarker • Journal • P1 data • Preclinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cryoablation and Arterial Infusion of SD-101 in Combination with Durvalumab and Tremelimumab (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of California, San Diego | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor