Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative HNSCC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGruppo Oncologico del Nord-Ovest
About this trial
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).
Eligibility criteria
Qualifiers
Patients of both genders, aged ≥18 years;
Signed written informed consent;
Primary histologically proven p16 negative squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx amenable to surgery with curative intent. p16 status will be assessed as surrogate marker for HPV infection only for oropharyngeal cancers. p16 status will be assessed using the CINtec p16 Histology assay (Ventana Medical Systems, Tucson, AZ, USA) with strong and diffuse nuclear and cytoplasmic staining in at least 70% of cells used as the cutpoint for positivity.
Clinical stage III-IV(M0) according to the VIII edition of AJCC staging system; recurrent/metastatic HNSCC, or previously treated HNSCC with local or systemic therapies, are not eligible for this study.
Disqualifiers
Patient has recurrent/metastatic disease;
Patient with locally advanced disease not amenable of surgery with curative intent;
Patient has received prior local or systemic treatment for HNSCC;
Patient with p16/HPV positive HNSCC;
Trial design
Treatments tested in this trial
- Niraparib
Treatment groups
49 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov