Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative HNSCC

We propose a window of opportunity trial to evaluate safety and efficacy of a short course of the study combination, composed by an Anti-PD-1 monoclonal antibody (Dostarlimab (TSR-042)) and a PARPi (Niraparib). The study population will be surgically resectable, HPV-negative (defined by p16 negative status) locally advanced HNSCC. Maintenance treatment will be then delivered, so to better integrate the therapeutic benefits of this drug combination. Response to neoadjuvant treatment will be evaluated by the rate of major pathologic response, morphologic, and functional imaging (MRI with functional evaluation -DWI). We anticipate that neoadjuvant and maintenance PARPi plus immunotherapy treatment could lead to a reduction of loco-regional recurrence (LRR) and distant metastasis (DM) rates in such a high-risk population. Furthermore, the window of opportunity portion of this trial will allow in vivo acquisition of valuable knowledge on mechanisms of action and primary resistance to Anti-PD-1 monoclonal antibody and PARPi in HNSCC. In this phase of the study, biological specimens will be collected (pre-treatment tumor biopsy, tissues from the surgical specimen, liquid biopsy, blood and saliva samples) as well as functional imaging (MRI).

NCT Number	NCT04681469
Lead Sponsor	Gruppo Oncologico del Nord-Ovest
Conditions	Head and Neck Squamous Cell Carcinoma
Enrollment	49 participants
Start Date	2021-02-08
Primary Completion	2023-06 (estimated)
Study Completion	2028-06 (estimated)
Updated on ClinicalTrials.gov	2022-08-04