Prime

80% of Head and Neck Squamous Cell Carcinoma are diagnosed at a locally/advanced stage. Treatment for locally/advanced Head and Neck Squamous Cell Carcinoma is mainly based on surgery combined with (chemo)radiotherapy. However, despite optimal locoregional treatment, disease relapse in 50% of cases. Once disease relapses, and is no longer amenable to locoregional curative treatment, prognosis worsens, with a 5 years survival rate that decreases from 50% to 15%. Immune Checkpoint inhibitor has proven activity, efficacy, and safety in either platinum naïve and platinum resistant Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. There are preclinical and clinical evidence about the enhanced sensitivity to combined treatment with a PARP inhibitor and an Immune Checkpoint inhibitor. The PRIME H & N Trial is a phase 2, single arm, open label, window of opportunity, clinical trial in which patients affected by locally advanced head and neck squamous cell carcinoma, p 16 negative, amenable for surgical treatment, will receive 2 or 3 cycles (based on clinical response) of neaoadjuvant treatment with PARP inhibitor (niraparib) 200 mg daily (oral compound) and Immune Check Point inhibitor (dostarlimab/TSR042) 500 mg (flat dose, intravenous), followed by surgery + (chemo)radiotherapy based on pathological staging as for clinical practice, and eventual adjuvant treatment with PARP inhibitor (niraparib) 200 mg daily (oral compound) and Immune Check Point inhibitor (dostarlimab/TSR-042) 500 mg (flat dose, intravenous) for 6 m

Main selection criteria are the following:
– histologically proven diagnosis of Head and Neck Squamous Cell Carcinoma of the oral
cavity, oropharynx, larynx, and hypopharynx candidate for surgery with curative
intent. Primary tumor sites different from the cited or Cancer of Unknown Primary
are not eligible
– p16 negative status (in case of oropharyngeal primary tumors)
– Stage III-IV (M0) according to AJCC TNM VIII edition
– Recurrent and/or Metastatic disease are not eligible
– Presence of at least one lesion target according to RECIST 1.1
– PS ECOG = 0-1; and adequate organ and bone marrow function
– Patients with a history of myelodysplastic syndrome or acute myeloid leukemia are
not allowed

The coprimary objectives are the activity in terms of major pathological response and the safety according with CTCAE v5.0 the study treatment niraparib + dostarlimab. Secondary objectives are the objective response rate, the progression-free survival, and to evaluate the presence of prognostic/predictive biomarkers through gene expression analysis, radiomic analysis, and immune infiltrates in saliva, blood, and tissue samples