guretolimod (DSP-0509) / Sumitomo Pharma - LARVOL DELTA

Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine. (PubMed, Cytokine) - "To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509...In this study, we compared the anti-tumor effects of EIK1001 and 5DEX-0509R, and analyzed its unique immune reaction against tumors to evaluate whether 5DEX-0509R is suitable for further clinical study...We also found that 5DEX-0509R synergistically suppresses tumors with oxaliplatin by changing M2 macrophages that cause oxaliplatin to become resistant to antitumor M1 macrophages. In addition, 5DEX-0509R caused a rapid but not sustained cytokine elevation in both rats and dogs. We believe 5DEX-0509R is worth pursuing for clinical trials."

Journal • Infectious Disease • Oncology • CD4

DSP-0509, a TLR7 agonist, exerted synergistic anti-tumor immunity combined with various immune therapies through modulating diverse immune cells in cancer microenvironment. (PubMed, Front Oncol) - "In summary, our study elucidated the effects of DSP-0509 on immune activity within the tumor microenvironment. These findings provided valuable insights that pave the way for the development of novel combination immunotherapy strategies."

Immune cell • Journal • Oncology • CD4 • CD8 • CTLA4 • GZMB • ICOS • IL10 • PRF1 • TNFA

DSP-0509, a TLR7 agonist, exerted synergistic anti-tumor immunity combined with various immune therapies through modulating diverse immune cells in cancer microenvironment (Front Oncol) - "..We combined DSP-0509 with an inhibitor targeting the receptor tyrosine kinase AXL. In bone marrow derived macrophages (BMDMs), the AXL inhibitor further amplified DSP-0509-stimulated TNFα secretion while reducing IL-10 secretion. As a final step, we evaluated the antitumor activity by combining DSP-0509 and the AXL inhibitor in an in vivo tumor model, which demonstrated increased efficacy."

Preclinical • Oncology

Targeting Tumor-Associated Macrophages with the Immune-Activating Nanomedicine for Achieving Strong Antitumor Activity with Rapid Clearance from the Body. (PubMed, ACS Nano) - "To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509...We also demonstrated that the antitumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. We believe that 5DEX-0509R generated by D-TAC technology can be a clinically applicable immunotherapy targeting the TLR signaling pathway."

Journal • Infectious Disease • Oncology • MRC1

TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation. (PubMed, BMC Immunol) - "These data suggest that TLR7 agonist, DSP-0509, can be a promising concomitant when used in combination with RT by upregulating CTLs activity and gene expression of effector molecules. This combination can be an expecting new radio-immunotherapeutic strategy in clinical trials."

Combination therapy • IO biomarker • Journal • Oncology • CD8 • GZMB • HAVCR2 • IL12A • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2 | N=36 | Terminated | Sponsor: Sumitomo Pharma America, Inc. | Completed ➔ Terminated; Sponsor's decision to terminate the development of the program due to changing landscape.

Combination therapy • IO biomarker • Metastases • Monotherapy • Trial termination • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2 | N=36 | Completed | Sponsor: Sumitomo Pharma Oncology, Inc. | Recruiting ➔ Completed | N=100 ➔ 36

Combination therapy • Enrollment change • Metastases • Monotherapy • Trial completion • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

DSP-0509, a systemically available TLR7 agonist, exhibits combination effect with immune checkpoint blockade by activating anti-tumor immune effects. (PubMed, Front Immunol) - "Although it is the only approved TLR7 agonist in cancer therapy, imiquimod is allowed to be administered with topical formulation. We confirmed that DSP-0509 enhanced the anti-tumor immune effects of anti-PD-1 antibody by inducing type I interferons via activation of dendritic cells and even CTLs. In conclusion, we expect that DSP-0509, a new TLR7 agonist that synergistically induces anti-tumor effector memory T cells with immune checkpoint blockers (ICBs) and can be administered systemically, will be used in the treatment of multiple cancers."

Checkpoint block • Checkpoint inhibition • Journal • Immune Modulation • Oncology • CD8

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Sumitomo Pharma Oncology, Inc. | Trial completion date: Sep 2025 ➔ Jan 2023 | Trial primary completion date: Dec 2023 ➔ Jan 2023

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Sumitomo Pharma Oncology, Inc. | Trial completion date: Dec 2023 ➔ Sep 2025

Combination therapy • Monotherapy • Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2; N=100; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Trial completion date: Sep 2021 ➔ Dec 2023; Trial primary completion date: Sep 2021 ➔ Dec 2023

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MRI • PD-L1

A first-in-human phase 1, multicenter trial of toll-like receptor (TLR) 7 agonist DSP-0509 as monotherapy and in combination with pembrolizumab in adult patients with advanced solid tumors (SITC 2019) - P1/2; "N/A"

Clinical • Combination therapy • Monotherapy • P1 data

[VIRTUAL] Modulation of immune suppressive cells by toll-like 7 agonist DSP-0509 which leads to potentiate anti-tumor activity of radiotherapy (AACR 2021) - "We showed two novel effects of DSP-0509 in this study, 1) modulation of immune suppressive cells and 2) extension of the survival of tumor-bearing mice in combination with RT, which would be explained by the additive CTL activation and memory T cell induction. Taken together, these results supported the hypothesis that combination of DSP-0509 with RT may enhance the anti-tumor immune activity by modulating CTL activity as well as immune suppressive cells."

IO biomarker • Oncology • CD4 • CD8 • FOXP3 • GZMB • IFNG • IL2RA • IL7R • ITGAM • TGFB1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2; N=100; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; N=60 ➔ 100

Clinical • Combination therapy • Enrollment change • Monotherapy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2; N=106; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Trial completion date: Jul 2020 ➔ Sep 2021; Trial primary completion date: Jun 2020 ➔ Sep 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI • PD-L1

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2; N=60; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; N=106 ➔ 60

Clinical • Combination therapy • Enrollment change • Monotherapy • Oncology • Solid Tumor

Boston Biomedical, Inc. highlights phase 1 data evaluating investigational WT1 cancer peptide vaccine DSP-7888 (ombipepimut-S) in patients with advanced malignancies at SITC 2019 (PRNewswire) - P1, N=24; NCT02498665; Sponsor: Boston Biomedical, Inc; “Of the 24 patients, four had stable disease and 21 patients were evaluable for WT1-specific cytotoxic T-lymphocyte (CTL) detection. In the evaluable population, WT1-specific CTL induction was observed in six of nine intradermal patients (66.7%) and five of 12 subcutaneous patients (41.7%). An intradermal dose of 10.5 mg was determined as the recommended phase 2 dose, consistent with the findings of a separate phase 1/2 study of DSP-7888 in patients with myelodysplastic syndrome. The most frequently observed adverse event was Grade 1 or 2 injection site reaction….The company will also present background information on an ongoing phase 1/2 clinical study evaluating DSP-0509…for the treatment of solid tumors.”

P1 data • P1/2 data

A Study of DSP-0509 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile (clinicaltrials.gov) - P1/2; N=106; Recruiting; Sponsor: Boston Biomedical, Inc; Phase classification: P1 ➔ P1/2; N=44 ➔ 106

Clinical • Combination therapy • Enrollment change • Monotherapy • Phase classification

Enhanced anti-tumor activity through a combination of intravenous injectable TLR7 agonist, DSP-0509 and immune checkpoint inhibitors (AACR 2019) - "In addition, the combination treatment with anti-CTLA-4 antibody also showed the anti-tumor activity with the increased IFN-gamma signature gene expression. These results suggest that combination of ICI with DSP-0509 resulted in anti-tumor activity by changing immunogenic “cold” to “hot” TME."

Checkpoint inhibition • IO Biomarker • PD(L)-1 Biomarker