926TiP - Phase II trial of enoblituzumab plus retifanlimab or tebotelimab in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN)

Background

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.

Trial design

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 1^st 12 pts. All patients will be followed for survival after receipt of the last dose of study drug.

Clinical trial identification

NCT04634825.

Editorial acknowledgement

Legal entity responsible for the study

MacroGenics, Inc.

Funding

MacroGenics, Inc.

Disclosure

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.