TREGCHECK 102: A study of tagmokitug (CHS-114) in combination with toripalimab and/or other treatments in participants with advanced solid tumors.

Abstract

TPS2689 Background: Advanced solid tumors frequently exhibit resistance to standard therapies, including immune checkpoint inhibition. Intratumoral Tregs have been associated with immune suppression, tumor progression and anticancer resistance. Intratumoral Tregs preferentially express CCR8 and are abundant in many solid tumors (Plitas 2020; Plitas 2016; Kidani 2022). Tagmokitug is a novel, selective cytolytic anti-CCR8 mAb designed to deplete CCR8+ Tregs and remodel the tumor microenvironment to promote antitumor immunity. Preclinical and phase 1 clinical studies show tagmokitug can significantly deplete CCR8+ intratumoral Tregs, increase immune activation and has antitumor activity in combination with a PD-1 inhibitor (Wang 2026; Worden 2025; Kapoor 2025). These findings warrant evaluation of tagmokitug in combination with toripalimab, a PD-1 inhibitor, and/or other anticancer therapies across multiple tumor types. Methods: This multicenter, open-label, phase 1b/2a study evaluates tagmokitug in combination with toripalimab and/or other therapies in adults with advanced solid tumors in 4 cohorts: gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma; second-line esophageal squamous cell carcinoma (ESCC); first-line ESCC; and advanced MSS/pMMR colorectal cancer. Eligible participants have histologically or cytologically confirmed advanced or metastatic solid tumors not amenable to curative therapy, measurable disease per RECIST v1.1, ECOG 0–1, and adequate organ function. Key exclusions include active autoimmune disease requiring systemic therapy, uncontrolled cardiovascular conditions, or other factors interfering with study participation. Tagmokitug is administered IV Q3W at pharmacologically active doses following toripalimab 240 mg IV and/or other anticancer therapies where indicated per protocol. Imaging assessments are performed every 6 weeks through week 24, every 9 weeks through week 51 and every 12 weeks through week 99. Patients continue treatment until disease progression, unacceptable toxicity, or withdrawal of consent. The primary objective is to evaluate the safety and tolerability of tagmokitug in combination with toripalimab and/or other anti-cancer therapies as measured by adverse events and laboratory abnormalities. Secondary endpoints include ORR, DOR, DCR, and PFS per RECIST v1.1, and assessment of PK and ADA. Exploratory endpoints include OS and biomarker analyses including evaluation of CCR8+ Tregs in tumors. Enrollment is ongoing. Approximately 150 participants are planned across all cohorts. Additional cohorts may be added based on emerging data. Clinical trial information: NCT06657144 .