A phase 1, first-in-human study of DS3610, a stimulator of interferon genes (STING) agonist antibody-drug conjugate (ADC), in patients with advanced/metastatic solid tumors.

TPS3159 Background: While immunotherapies have improved treatment for patients with advanced/metastatic solid tumors, there remains a need for novel therapies that can overcome resistance to existing therapies, enhance antitumor activity, and delay disease progression. Promoting the innate immune response through activation of the endoplasmic reticulum adaptor protein stimulator of interferon genes (STING) has been associated with antitumor activity. DS3610 is an antibody–drug conjugate (ADC) comprising an anti-epidermal growth factor receptor (EGFR) monoclonal antibody attached to an immunomodulatory payload that acts as an agonist of STING. EGFR is a transmembrane receptor tyrosine kinase that is overexpressed in a broad range of solid tumors. DS3610 is designed to deliver the STING agonist payload directly to the tumor microenvironment, activating immune cells such as antigen-presenting cells and T cells, and inducing immune targeting of cancer cells. The antibody component has novel Fc modifications designed to reduce the risk of class-specific adverse events, such as systemic cytokine release. Methods: DS3610-071 (NCT07159126) is a Phase 1, first-in-human, open-label, global, dose-escalation study of DS3610 (N≈70). Patients must be adults with advanced or metastatic solid tumors and be intolerant to standard-of-care therapies or have disease that has relapsed after or is refractory to such therapies. Eligible tumor types include non-small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial carcinoma, colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer, biliary tract cancer, and uterine cancer. Patients must have measurable disease per RECIST 1.1; an ECOG performance status of 0, 1, or 2; and be willing and able to provide a pretreatment or archival tumor tissue sample. Patients will receive DS3610 at escalating doses. The primary objectives are to assess the safety and tolerability of DS3610 and to determine the recommended dose(s) for expansion for further evaluation of DS3610. Safety endpoints include identifying dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include the assessment of DS3610 immunogenicity, based on the prevalence and incidence of antidrug antibodies, and the evaluation of DS3610 pharmacokinetics. Exploratory endpoints include evaluating the efficacy of DS3610 and identifying biomarkers that may be associated with clinical benefit. Enrollment is ongoing. Clinical trial information: NCT07159126 .