Dr Bockorny on the Rationale for Targeting CCR8 in Solid Tumors

"CCR8 is a great marker of intratumoral Tregs, as [opposed] to Tregs in the periphery, making CCR8 a very attractive immunotherapy target."

Bruno B. Bockorny, MD, a gastrointestinal medical oncologist at Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, discussed the rationale for evaluating the anti-CCR8 antibody denikitug (GS-1811) in patients with solid tumors, including gastrointestinal cancer.

A primary challenge in modern oncology is the presence of regulatory T cells (Tregs), which serve as major drivers of immunosuppression within the tumor microenvironment, Bockorny began. Previous research has demonstrated that the infiltration of Tregs can significantly worsen a patient's prognosis by dampening the body's natural immune response against the malignancy.

The clinical interest in denikitug stems from its target, CCR8, which has emerged as a highly specific marker for intratumoral Tregs as opposed to those found in the peripheral blood, Bockorny explained. This distinction makes CCR8 an attractive immunotherapy target, as it allows for the selective depletion of immunosuppressive cells directly within the tumor, he asserted.

Denikitug is a monoclonal antibody specifically designed to target CCR8 and enhance antibody-dependent cellular cytotoxicity, thereby clearing these inhibitory cells and potentially restoring an active immune environment.

To assess the safety and efficacy of this approach, Bockorny and his colleagues conducted a phase 1, first-in-human, dose-escalation study (NCT05007782). The trial evaluated denikitug monotherapy or in combination with an anti–PD-L1 agent in patients with advanced solid tumors who experienced disease progression after receiving standard therapies.

Interim data from the ongoing study were shared at the 2026 AACR Annual Meeting and focused on 2 monotherapy groups: Part A, which involved dose escalation across 5 levels (1 to 100 mg every 3 weeks), and Part B, which utilized a paired biopsy cohort in select tumor types.