856P - Safety of neoadjuvant PARP inhibitor and immunotherapy in locally advanced HPV-negative head and neck squamous cell carcinoma (PRIME H&N Study)

Background

Local relapse and/or distant failure are a clinical issue in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). The PRIME trial evaluates combination of dostarlimab (D) and niraparib (N) as neoadjuvant and adjuvant treatment for LA HPV-negative HNSCC. Here we present the safety of the neoadjuvant part of the trial.

Methods

This is a phase II, single arm, multicenter trial. Patients (pts) with HPV-negative, stage III-IV HNSCC, amenable for surgical treatment received: N 200 mg/day (day -49 to day -21) and D 500 mg iv (day -49 and day -28). On day -21, clinical and radiological evaluations were performed and in case of no response, pts were addressed to curative surgery +/- adjuvant (chemo)radiotherapy ((C)RT); otherwise, pts continued treatment until day -7 and then were addressed to curative surgery +/- adjuvant (C)RT. The primary endpoint was the major pathological response. Secondary endpoints were activity and safety.

Results

From 3/2021 to 12/2023, we enrolled 39 pts; 93 treatment-related (TR) adverse events (AEs) of any grade were reported (79.6% G1-2 and 20.4% G3-4). Overall, 74.4% of the pts experienced TRAEs (67% of G1-2 and 33% of G3-4) during neoadjuvant phase. Overall, TRAEs were 20.4% gastrointestinal (1.1% G3-4), 20.4% AST/ALT increase (4.3% G3-4), 11.8% hematological (7.5% G3-4), 10.8% systemic (1.1% G3-4), 10.8% cutaneous (all G1-2), 4.3% endocrinological (all G1-2), 2.2% ocular (1.1% G3-4) and 15% others (1.1% G3-4). Delay in surgery was observed [GSK1] [PB2] in 1 pts (10 days) due to elevation of CK and troponin T, that were not linked to any cardiac event. In terms of surgical toxicities, 4 pts experienced G3 AEs that were not considered related to treatment: postoperative orocutaneous fistula; flap death; necrosis of the flap skin; postoperative haemorrhage with loss of the flap.

Conclusions

The PRIME trial demonstrated acceptable safety and tolerability of study treatment. Translational data and primary endpoint analysis are still ongoing to define study treatment efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Foundation Gruppo Oncologico Nord Ovest (GONO).

Funding

Both Funding and Product for this study was provided by GSK. GSK was provided the opportunity to provide a courtesy review of the preliminary version of this publication for accuracy only, but the authors are solely responsible for final content and interpretation.

Disclosure

All authors have declared no conflicts of interest.