Domain Therapeutics has achieved a significant clinical milestone by dosing the first patients in its Phase I/II DOMISOL trial of DT-7012, a novel anti-CCR8 monoclonal antibody designed to deplete regulatory T cells (Tregs) in solid tumors. The first-in-human study represents the company's second fully proprietary asset to enter clinical development.
Novel Mechanism Targets Immunosuppressive Environment
DT-7012 is engineered to selectively target CCR8, a receptor predominantly expressed on Tregs within the tumor microenvironment. The therapy leverages potent antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mechanisms to eliminate these immunosuppressive cells, potentially transforming the tumor microenvironment into a more immunocompetent state.
"DT-7012 stands out with its unique and differentiating properties, offering unprecedented selectivity in depleting intratumoral Tregs while simultaneously improving overall immune system function," said Stephan Schann, Chief Scientific Officer of Domain Therapeutics. "These features are critical for effective cancer immunotherapy, positioning DT-7012 as a promising candidate to overcome immune resistance and bring hope to patients with limited treatment options."
Differentiated Properties Address Clinical Challenges
The antibody exhibits several distinguishing characteristics that set it apart from other CCR8-targeting therapies in clinical development. DT-7012 demonstrates broader binding across CCR8 variants, extending its therapeutic reach across diverse immunosuppressive populations. Additionally, the therapy maintains depletion efficiency even in CCL1-rich environments, preventing CCR8 internalization and ensuring sustained Treg depletion in challenging tumor microenvironments.
Addressing Unmet Medical Need in Cancer Immunotherapy
The development of DT-7012 addresses a critical gap in cancer treatment where regulatory T cells suppress immune responses, driving resistance to immune checkpoint inhibitors (ICIs) and limiting their effectiveness. Professor Vinod Ganju, Principal Investigator at Peninsula and Southeast Oncology (PASO), emphasized this unmet need: "Immune checkpoint inhibitors have revolutionized cancer treatment, yet a significant unmet need remains as Tregs suppress immune response, driving resistance to ICIs and limiting their effectiveness."
Clinical Trial Design and Implementation
The DOMISOL study is structured as an open-label, multicenter Phase I/II, first-in-human dose-escalation and cohort-expansion trial. The study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of DT-7012 in adult patients with selected advanced solid tumors.
The trial is being conducted in Australia, with initial clinical sites including Peninsula and Southeast Oncology (PASO) and Cabrini Health in Melbourne. Additional centers are expected to come online in the coming months, with the trial registered under NCT06819735.
Strategic Positioning in Competitive Landscape
CCR8 has emerged as a highly competitive target, drawing significant interest across the pharmaceutical industry, including from leading pharmaceutical companies. Sean A. MacDonald, Chief Executive Officer of Domain Therapeutics, noted that "dosing of the first patients in the DOMISOL trial represents a significant milestone, as DT-7012 becomes our second fully proprietary asset to enter the clinic, underscoring our proven ability to translate cutting-edge GPCR biology into high value differentiated products."
The initiation of this trial in Australia aligns with Domain's strategy to accelerate clinical development and strengthens momentum behind the company's pipeline of drug candidates targeting G protein-coupled receptors (GPCRs), a crucial class of drug targets that represent 30-35% of all marketed drugs despite existing therapies targeting only 10% of total potential GPCR targets.
