Abstract CT038: Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors

Abstract Background: Selective depletion of intratumoral regulatory T cells (itTregs) is an attractive immunotherapy strategy. CHS-114 is a selective, cytolytic anti-CCR8 mAb designed to deplete immunosuppressive CCR8+ itTregs and remodel the tumor microenvironment (TME) to promote antitumor immunity. We present interim data from an ongoing phase 1 study focused on recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Methods: This multicenter ongoing phase 1 study (NCT05635643) enrolled adults whose disease progressed on or after standard therapies into 3 arms (Q3W IV cycles): Arm 1a (CHS-114 dose escalation from 5 to 1200 mg); Arm 1b (2 dose levels [DL1 or DL2] of pharmacologically active CHS-114); Arm 2 (CHS-114 DL1 or DL2 + toripalimab [tori] 240 mg). Arm 1a evaluated patients (pts) with solid tumors; Arms 1b and 2 evaluated pts with HNSCC, and Arm 1b required paired tissue biopsies. Primary objectives were to optimize the CHS-114 dose(s) for expansion and evaluate the safety of CHS-114 + tori. Secondary objectives were to evaluate the safety, PK and antitumor activity of CHS-114 ± tori and assess changes in Tregs and CD8 T cells in paired tumor biopsies and other immune biomarkers. Results: Two DLs were selected for dose optimization based on safety, peripheral CCR8+ Treg depletion, PK and biomarker data. As of October 20, 2024, 30 pts received CHS-114 (Arms 1a [n=20], 1b [n=3], 2 [n =7]). Rapid and sustained peripheral blood CCR8+ Treg depletion was observed at all DLs. No dose-limiting toxicities were reported. CHS-114 treatment-related adverse events (TRAEs) occurred in 40% of pts in Arms 1a, 67% in 1b, and 100% in 2. The most common TRAEs were: fatigue, sweats and nausea (33% each) in Arm 1b and fatigue, pain, infusion-related reaction (IRR), ALT and/or AST increased (29% each) in Arm 2; there were no serious TRAEs or TRAEs leading to death in Arms 1b or 2. The most common Grade ≥3 TEAEs were wound infection, anemia, swelling face, hyponatremia (33% each) in Arm 1b and wound infection, hypoxia, oropharyngeal fistula, IRR, ALT increased, blood alkaline phosphatase increased (14% each) in Arm 2. In on-treatment tumor biopsies, CCR8+ itTreg depletion with increased CD8+ T cells infiltration was observed, indicating favorable TME remodeling. Increased immune activation biomarkers were observed in blood. In Arm 2, one confirmed PR occurred with CHS-114 DL2 + tori (after the data cutoff date). Conclusions: CHS-114 with and without tori had an acceptable safety profile, depleted CCR8+ Tregs and increased CD8 T cells in the TME in pts, supporting further evaluation of CHS-114 in combination with other drugs including tori. Updated safety, efficacy, tumor biopsy and biomarker data will be presented. Citation Format: Francis Worden, Cristina Rodriguez, Amita Patnaik, Justin Call, A. Dimitrios Colevas, Ammar Sukari, Trisha Wise-Draper, Nabil Saba, Koho Iizuka, Hong Tang, Varun N. Kapoor, Douglas Adkins. Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT038.