435 Pegasus HNSCC, a platform study of SAR444245 (THOR-707, a pegylated recombinant non-alpha IL-2) with anti-cancer agents in patients with recurrent/metastatic head and neck squamous cell carcinoma

Background SAR444245 (THOR-707) is a recombinant human IL-2 molecule that includes a PEG moiety irreversibly bound to a novel amino acid via click chemistry to block the alpha-binding domain while retaining near-native affinity for the beta/gamma subunits. In animal models, SAR444245 showed anti-tumor benefits, but with no severe side effects, both as single agent and when combined with anti-PD1 comparing with historical data from aldeslukin. Preclinical study demonstrated SAR444245 enhances ADCC function of cetuximab. The HAMMER trial, which is the FIH study shows preliminary encouraging clinical results: initial efficacy and safety profile with SAR444245 monotherapy and in combination with pembrolizumab or with cetuximab support a non-alpha preferential activity, validating preclinical models. The Pegasus Head and Neck Ph 2 study will evaluate the clinical benefit of SAR444245 in combination with other anticancer therapies for the treatment of patients with R/M HNSCC. Methods The Pegasus Head and Neck will enroll approximately 272 patients in 4 separate cohorts concurrently. In cohorts A1 & A2, 1L R/M HNSCC patients will receive SAR444245 + pembrolizumab, or SAR444245+ pembrolizumab+ cetuximab respectively. In cohort B1 & B2 patients with 2/3L R/M HNSCC failed a checkpoint based regimen & a platinum containing regimen will receive SAR444245 + pembrolizumab, or SAR444245 + cetuximab. Patients to be enrolled in cohort B2 need to be cetuximab-naive in R/M setting. SAR444245 is administered intravenously IV at a dose of 24 ug/kg Q3W until disease progression (PD) or completion of 35 cycles. Pembrolizumab is administered at a dose of 200 mg Q3W until PD or completion of 35 cycles. Cetuximab is administered at a dose of 400/250 mg/m2 QW until PD. The study primary objective is to determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary objectives include confirmation of dose and safety profile, assess other indicators of antitumor activity, and assess the pharmacokinetic profile and immunogenicity of SAR444245. The study will be conducted in the US, Canada, France, Germany, Italy, Netherlands, Poland, South Korea, Spain and Taiwan. Acknowledgements The Pegasus Head and Neck study is sponsored by Sanofi.