Head and neck cancer accounts for >650,000 new cases and nearly 330,000 annual deaths worldwide as of 2018. Patients with R/M SCCHN have a poor prognosis with median overall survival <1 year. PD-1 and PD-L1 blockade has shown antitumor activity in advanced SCCHN. Enoblituzumab is an investigational Fc-modified monoclonal antibody that binds B7-H3. B7-H3 is overexpressed in many cancers including SCCHN, but not in most normal tissues. Retifanlimab (INCMGA00012) is an investigational anti-PD-1 monoclonal antibody. Tebotelimab is an investigational, Fc-bearing bispecific, tetravalent DART® molecule designed to bind PD-1 and LAG-3 and sustain/restore function of T cells. Tebotelimab has demonstrated improved T-cell responses in vitro beyond that observed with anti-PD-1 and anti-LAG-3 antibodies alone or in combination. In a phase I study of enoblituzumab plus pembrolizumab, study drug was well tolerated. The overall response rate of PD-1/PD-L1 inhibitor-naïve SCCHN patients (post platinum) was 33% (6/18), including 1 confirmed complete and 5 confirmed partial responses, providing a rationale for further development of this combination in R/M SCCHN.
This is an open-label, non-randomized study in first-line treatment of patients with R/M SCCHN, with first patient enrolled in March 2021. Approximately 50 patients CPS >=1 will receive enoblituzumab 15 mg/kg plus 375 mg retifanlimab and 30 patients CPS<1 will receive enoblituzumab 15mg/kg plus 600 mg tebotelimab. Dosing is Q3W with tumor assessment at end of Cycle 2 and every 3 cycles thereafter. In the tebotelimab cohort, safety data will be reviewed for dose limiting toxicities through Cycle 2 Day 7 on the 1st 12 pts. All patients will be followed for survival after receipt of the last dose of study drug.
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J. Sun: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc. D. Loo: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc.; Financial Interests, Personal, Stocks/Shares: MacroGenics, Inc. C. Bohac: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc.; Financial Interests, Personal, Stocks/Shares: MacroGenics, Inc. All other authors have declared no conflicts of interest.