704TiP SAR445256 (KY1044) in combination with atezolizumab in patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)

Abstract

SAR445256 (KY1044) is a fully human IgG1 targeting ICOS with a dual mechanism of action: dose dependent depletion of ICOShigh Tregs in tumor microenvironment and activation of ICOSlow Teff. NCT03829501 is the first in human study testing safety, efficacy, and pharmacological properties of SAR445256 with/without atezolizumab in PD-L1 naïve or pretreated pts with advanced malignancies. Dose escalation part was guided by an adaptive dose-finding method and Ph 1 enrichment part was included for a better understanding of safety, tolerability, preliminary anti-tumor efficacy and PK/PD relationships of SAR445256 in combination with atezolizumab. Selected Ph2 dose was 8mg with atezolizumab 1200mg, both given IV, Q3W. In Ph1, a 59-year-old male pt with HPV+ HNSCC who progressed on 5 prior lines of therapy (including nivolumab), experienced a PR (42% tumor shrinkage), still holding as of C26D1, and on treatment for >20 months as of 10Feb2022. Strong expression of ICOS on intratumoral Tregs in head and neck cancer as well as the promising clinical activity previously reported suggest HNSCC to be favorable indication for SAR445256. Ph2 cohorts (2 cohorts, PD-L1 naïve and pretreated) are being initiated in HNSCC pts. Approximately 40 pts will be enrolled in each cohort. Key inclusion criteria: anti -PD-L1 therapy naïve and pretreated, 1-2 prior lines of systemic therapy for advanced disease, histologically documented advanced/metastatic malignancies, measurable disease by RECIST 1.1, site of disease amenable to biopsy. Key exclusion criteria: CNS metastases, active autoimmune disease, significant heart disease and/or QT prolongation, steroid therapy, or any immunosuppressive therapy. Efficacy measures will be performed as per RECIST 1.1 Q8W for the first 16 weeks and then Q12W, while AEs will be classified according to CTCAE v5. SAR445256 was well tolerated and showed initial signs of activity, in a HNSCC pt who received multiple prior lines of therapy. Ph2 assessment is planned in 2 cohorts: HNSCC pts PD-L1 naïve and pretreated. Note: Atezolizumab will continue to be provided by Roche for the RP2D part of this study as well. 1. Sainson R et al 2020. 2. Patel MR et al 2021. NCT03829501. Mukul Rastogi, PhD of Sanofi. Sanofi.