A phase 1/2 open-label study of KY1044, an anti-ICOS antibody with dual mechanism of action, as single agent and in combination with atezolizumab, in adult patients with advanced malignancies

2624 Background: KY1044, is a fully human IgG1 anti ICOS antibody designed to stimulate Teffs and to deplete ICOS high Tregs in the tumor microenvironment. Methods: Patients with advanced/metastatic malignancies received escalating doses of KY1044 as a single agent and in combination with atezolizumab 1200 mg by IV infusion every 3 weeks until disease progression or unacceptable toxicity. Dose escalation was guided by a modified toxicity probability interval design. The primary objective was to determine safety, tolerability, and maximum tolerated dose. Cohorts that were tolerated were later enriched with more subjects. AEs were classified according to CTCAE v5 and efficacy measures performed according to RECIST v1.1 every 8 weeks for the first 16 weeks and then every 12 weeks. Results: As of 16-Dec-2020, a total of 103 patients have been enrolled in the study (38 patients as monotherapy in 6 cohorts at doses ranging from 0.8 to 240 mg and 65 in combination with atezolizumab in 5 cohorts at doses 0.8 – 80 mg). 63% and 55% of patients received ≥4 prior anti-cancer therapies in the single agent and combination cohorts, respectively. All cohorts were completed without DLTs during the first 21 days of treatment. In the KY1044 single agent cohorts, 47.4% of patients experienced treatment-related AEs (TRAEs), all were grades 1 or 2. In the combination cohorts, TRAEs were observed in 58% of patients. Most of the TRAEs were grade 1 or 2 apart from 8 TRAEs that were ≥grade 3 occurring in 43 weeks (range 45 to 66 weeks). Conclusions: KY1044 is well tolerated as single agent and in combination with atezolizumab. Objective responses have been observed in this phase 1 part of the study. The phase 1 expansion and phase 2 part of the study is ongoing. Clinical trial information: NCT03829501.