A phase 1/2, first-in-human, open-label, dose-escalation and -expansion study of TAK-188, a novel antibody-drug conjugate (ADC) targeting CCR8 + regulatory T cells, in adult patients with locally advanced or metastatic solid tumors.

TPS3155 Background: Regulatory T cells (Tregs) are key contributors to an immunosuppressive tumor microenvironment (TME). Their abundance in solid tumors is often linked to poor patient prognosis, decreased overall survival, and resistance to immunotherapy. Tumor-infiltrating Tregs express high levels of chemokine receptor CCR8, making CCR8 an attractive target for immunotherapy. TAK-188 is a first-in-class anti-CCR8 ADC that aims to enhance patients’ own antitumor activity by selectively eliminating CCR8-positive Tregs within the TME. It uses a novel amanitin payload capable of killing both actively dividing and non-dividing cells and is linked to the antibody via a cleavable linker. The nonclinical toxicology profile demonstrated monitorable and partially-to-completely reversible toxicities at doses exceeding projected clinically efficacious exposures. Preclinical evaluation of TAK-188 showed robust and deep depletion of CCR8 + cells in vitro and in vivo , and demonstrated anti-tumor activity as a single agent in non-clinical models (Casson et al. AACR 2026). Methods: This phase 1/2 study (NCT07205718) is enrolling adult patients with locally advanced or metastatic solid tumors known to express high levels of CCR8 on Tregs in the TME (gastroesophageal adenocarcinoma GC and esophageal squamous cell carcinoma ESCC, pancreatic ductal adenocarcinoma, non-squamous and squamous non-small cell lung cancer NSCLC, head 62–176 patients across ~35 sites in cohort-expansion). Clinical trial information: NCT07205718 .