iTeos Therapeutics Announces New Preliminary Data Indicating Clinical Activity with its Anti-TIGIT Antibody, EOS-448, at the AACR Annual Meeting 2021 - Seite 2

Summary of the Data Presented

The objective of the dose escalation portion of the ongoing EOS-448 trial, presented at AACR, is to evaluate primary objectives of safety and tolerability, and secondary objectives of pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of EOS-448 as a monotherapy in patients with advanced solid tumor cancers. As of the data cut-off (December 31, 2020), the trial had enrolled 22 advanced cancer patients with solid tumors for whom no standard treatment was available. The patients received EOS-448 intravenously (IV) once every two weeks (Q2W) or once every four weeks (Q4W) according to their dose and schedule allocation. Doses of 20, 70, 200, 700 mg Q2W and 1400 mg Q4W were evaluated. Since the data cut-off for the AACR poster, as of March 9, 2021, an additional 11 patients have received single agent EOS-448. In addition to the five dose levels which were described at AACR, patients have also received doses of 400mg Q4w and 700mg Q4w.

EOS-448 was generally well-tolerated at all tested doses in patients with advanced cancer. Preliminary evidence of clinical activity as a monotherapy, including a confirmed partial response in one pembrolizumab-refractory melanoma patient and disease stabilization in nine patients, was also observed. The most common treatment related adverse events were itching, infusion-related reactions, fatigue, rash and fever, and one treatment related serious adverse event, a grade 2 systemic inflammatory response, was observed. As of March 9, 2020, two additional treatment-related serious events have been reported: Grade 2 Systemic Inflammatory Response and Grade 3 infusion-related reaction.

PK assessments indicated a linear and dose-proportional response and PD assessments showed complete target engagement. Biomarker analyses showed evidence of FcγR engagement, as demonstrated by a reduction in suppressive immune cells and immune cells considered to be exhausted in the blood, including TIGIT⁺ regulatory T cells (Tregs) and TIGIT⁺ CD8 T cells, with only a slight reduction in the total CD8⁺ T cell count. A shift towards a more functional immune response was observed, with a two-fold increase in the ratio of CD8⁺ T cells to Treg and a four-fold increase in the ratio of CD8⁺ TIGIT^- T cells to CD8⁺ TIGIT⁺ T cells.