A pilot study of neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab in patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Dunn Lara , Sherman Eric Jeffrey , Ho Alan Loh , Ganly Ian , Riaz Nadeem , Morris Luc , Hung Kin Wai (Tony) , Kriplani Anuja , Cracchiolo Jennifer R. , Cohen Marc , Boyle Jay , Patel Snehal G. , Haque Sofia , Katabi Nora , Ghossein Ronald A , McBride Sean Matthew , Michel Loren S. , Wong Richard J. , Lee Nancy Y. , Pfister David G. 
Published: June 2022

TPS6109 Background: Definitive treatment of locally advanced HNSCC can require radical surgery and reconstruction often resulting in unacceptable functional consequences. Radiotherapy, often with concurrent chemotherapy, is administered postoperatively to achieve the best chance for cure. Induction chemotherapy has previously been shown to reduce the extent of surgical resection and need for adjuvant radiation (RT). The purpose of this trial is to evaluate if an induction regimen combining cytotoxic chemotherapy, EGFR targeting, and immune checkpoint blockade can pathologically downstage resectable HNSCC sufficiently to decrease surgical morbidity and justify omission of adjuvant RT-based therapy. Compared to standard docetaxel, cisplatin, and 5-FU (TPF), docetaxel, cisplatin, and cetuximab (TPC) has been shown to be a therapeutic alternative with a more favorable toxicity profile. Targeting PD-1 alone can induce significant pathologic responses in resectable HNSCC patients. Combining PD-1 inhibitors with cetuximab has shown promising activity in incurable HNSCC; cetuximab may optimize the tumor immune microenvionment for PD-1 therapy by stimulating IFN-gamma secretion to increase dendritic cell maturation and CD8 T cell expression of PD1. Based on this rationale, we are evaluating the novel induction regimen of platinum, docetaxel, cetuximab plus cemiplimab (anti-PD1 antibody). Methods: This is a 10-patient pilot study for locally advanced, resectable HNSCC patients for whom standard management requires adjuvant RT +/- chemotherapy. Patients will receive neoadjuvant treatment with a loading dose of cetuximab and cemiplimab followed by 3 cycles of cisplatin or carboplatin, docetaxel, cetuximab and cemiplimab followed by definitive surgical resection of the primary site +/- neck dissection(s). Post-operative RT +/- radiosensitizing agent(s) will be administered per standard of care (SOC) based on pathologic staging (rather than clinical staging at presentation). If the pathologic stage following induction and surgery is ypT0-2N0 without adverse features, adjuvant RT will not be administered and 6 months of adjuvant cemiplimab will be given. Otherwise, patients will receive SOC adjuvant RT-based treatment. The primary endpoint is safety and tolerability. Secondary endpoints include feasibility assessed by the number of patients whose definitive surgery was delayed due to toxicity and quantifying the number in whom clinical to pathologic downstaging is achieved and the planned surgery and/or need for adjuvant-RT based therapy is modified. Exploratory endpoints include evaluating the association between biomarkers in the tumor microenvironment and peripheral blood with pathologic response. 8 of 10 patients have been enrolled. Clinical trial information: NCT04722523.