DA-4505 / Dong-A - LARVOL DELTA

Conditional knockout of the aryl hydrocarbon receptor in macrophages and dendritic cells enhanced antigen presentation and T cell activation, thereby synergistically improving anti-cancer effects in combination with anti-PD-1 (AACR 2025) - "Knocking out AhR in myeloid cells enhances immune responses, thereby increasing the anti-tumor efficacy of aPD-1 combination therapy."

Combination therapy • IO biomarker • Lung Cancer • Oncology • Solid Tumor • CD4 • GZMB • IFNG • ITGAX

Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DA-4505 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Dong-A ST Co., Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2030 ➔ Oct 2029

Enrollment open • Trial completion date • Oncology • Solid Tumor

Enhanced anti-cancer efficacy of the AhR Inhibitor DA-4505 in combination with anti-PD-1 treatment: Attenuation of lung metastasis and elimination of tumor (AACR 2024) - "The AhR inhibitor, DA-4505, has demonstrated enhanced anti-tumor efficacy when administered in combination with anti-PD-1. Furthermore, it not only promoted tumor elimination but also demonstrated significant efficacy in inhibiting metastasis. This study highlights the potential of combining AhR inhibitors with immunotherapies for clinical treatment."

Clinical • Combination therapy • IO biomarker • Colon Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DA-4505 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Not yet recruiting | Sponsor: Dong-A ST Co., Ltd.

Combination therapy • Metastases • New P1/2 trial • Oncology • Solid Tumor

Dong-A ST advances phase 1/2a study of cancer immunotherapy (Korea Biomedical Review) - "Dong-A ST said Monday that it has received IND approval for a phase 1/2a clinical trial of its immuno-oncology drug, DA-4505, from the Ministry of Food and Drug Safety (MFDS), to treat solid tumors. The study will evaluate the safety and efficacy of DA-4505 monotherapy or in combination with the PD-1 immune checkpoint inhibitor, pembrolizumab, in adult patients with locally advanced or metastatic solid tumors."

New P1/2 trial • Solid Tumor

A novel AhR inhibitor ‘DA-4505’ improved the anti-cancer efficacy of surgical and chemotherapy via synergistic anti-tumor effects of aPD-1 (AACR 2023) - "Here, we propose that a best-in-class AhR inhibitor, DA-4505, improves anti-tumor efficacy via modulation of tumor immune surveillance compared to BAY2416964, an AHR antagonist drug candidate being studied in the clinical phase. To evaluate anti-tumor effects of DA-4505 and BAY2416964, the two AhR inhibitors were dosed at 10 mg/kg once daily alone or in combination with aPD-1 (10 mg/kg) in surgical and chemotherapy models, and a PDX model (YHIM2004)...A tumor reduction was shown by treating DA-4505 alone or in combination with pembrolizumab compared to vehicle group (P<0.05)... The AhR inhibitor DA-4505 demonstrated an improvement in anti-tumor efficacy. In addition, it has shown a synergistic effect when combined with aPD-1. Discoveries from this study provide a preclinical rationale for future clinical implications in solid tumor."

Clinical • Oncology • Solid Tumor • CCL7 • CCL8 • CD8

Anti-tumor effect of DA-4505, a novel AhR antagonist as an immunotherapy in the tumor microenvironment (AACR 2023) - "Secondly, DA-4505 reduced the immunosuppressive mechanisms by regulating Treg and M2-macrophage. Thus, our data demonstrate the potential of AhR as a promising therapeutic target for cancer immunotherapy as well as proposing DA-4505 as a novel therapeutic agent for both mono and aPD-1 combinatory therapeutic scheme."

Biomarker • Tumor microenvironment • Oncology • CD8 • CYP1A1 • IDO1 • IFNG • IL2 • TDO2