NCT04681469

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

Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Sponsor: Gruppo Oncologico del Nord-Ovest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

The entire patient population will receive the following treatment: * Niraparib 200 mg/day: day -49 to day -21; * Dostarlimab 500 mg iv: day -49 and day -28; At day -21, clinical evaluation will be performed and the patient will be directed to surgery with exclusion from the study in case of progressive disease. Radiological assessment will be performed according to the physician's judgement. If no clinical evidence of disease progression, the following schedule will be carried out: * Niraparib 200 mg/day day -21 to day -7 * Dostarlimab 500 mg iv: day -7 * Clinical and radiological evaluation with Diffusion Weighted Imaging Magnetic Resonance Imaging (DWI MRI) of the disease at day -1 (± 3 days); * Surgery (original margin) day 0 (± 3 days, within 72 hours from radiological assessment); Following surgery, patients included in the study will undergo standard postoperative (chemo)radiotherapy according to pathologic report. Furthermore, the following schedule will be carried out, in a period comprised between 2 and 6 weeks after the end of radiation therapy: * Maintenance Niraparib, 200 mg/day for 6 months * Maintenance Dostarlimab, 500 mg iv q3W for the first four cycles and 1000 mg iv Q6W thereafter for 3 months. Before starting this adjuvant treatment phase, inclusion and exclusion criteria of the protocol should be re-assessed and every patient should meet these criteria. Then the patient will start the follow up period, consisting in clinical visits every 3 months for the first year and every 4 months for the second year, then every year. After this period, the patient will be followed according to clinical practice in each site. In each follow up, clinical evaluation with fiberendoscopic assessment will be carried out; moreover, radiological imaging with MRI will be performed every other visit. CT scan of abdomen and thorax or PET/CT will be requested at 12 and 24 months after treatment end. In any case, radiological exams will be requested in case of any doubts of recurrence or late toxicity.

Conditions

• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Niraparib	For all patient's population: * Niraparib 200 mg/day: day -49 to day -21; * Dostarlimab 500 mg iv: day -49 and day -28; At day -21, clinical evaluation will be performed and the patient will be directed to surgery with exclusion from the study in case of progressive disease. Radiological assessment will be performed according to the physician's judgement. If no clinical evidence of disease progression: * Niraparib 200 mg/day: day -21 to day -7 * Dostarlimab 500 mg iv: day -7 * Radiological assessment (day -1, ± 3 days), * Surgery (original margin) at day 0 (±3 days) * Standard postoperative (chemo)radiotherapy according to pathologic report; * Maintenance Niraparib, 200 mg/day for 6 months * Maintenance Dostarlimab, 500 mg iv q3W for the first four cycles and 1000 mg iv Q6W thereafter for 3 months.

Timeline

• Start date: 2021-02-08
• Primary completion: 2023-06-01
• Completion: 2028-06-01
• First posted: 2020-12-23
• Last updated: 2022-08-04

Locations

1 site across 1 country: Italy