Phase II multicenter randomized trial to assess the efficacy and safety of first line nivolumab in combination with paclitaxel in subjects with R/M HNSCC unable for cisplatin-based chemotherapy (NIVOTAX): A TTCC study

TPS6086 Background: Nivolumab is the standard of care for patients (pts) with R/M HNSCC in the platinum-refractory setting. Up to 20% of R/M HNSCC pts are ineligible for cisplatin-based CT due to poor performance status and/or comorbidities. ERBITAX (weekly cetuximab + paclitaxel) is a recommended regimen for this patient population according to the Spanish Society of Medical Oncology guidelines. Preclinical data suggests a role for paclitaxel as immuno-modulator, mainly by increasing tumor infiltrating CD8+ (Galluzzi L., et al 2015). NIVOTAX trial aims to evaluate efficacy and safety of nivolumab + paclitaxel vs ERBITAX as first-line treatment for R/M HNSCC pts with platinum-refractory disease or ineligible for platinum-based chemotherapy. Methods: NIVOTAX (NCT04282109) is a randomized, open-label, multicenter, phase II trial sponsored by the Spanish Group of Head and Neck Cancer Treatment (TTCC) including R/M HNSCC pts not amenable for curative-intent therapy, previously untreated for R/M disease and not candidates for cisplatin-based chemotherapy. Population is distributed in 3 Groups: 1= Platinum-refractory; 2=Platinum-sensitive but unable to receive cisplatin due to: Karnofsky performance status (KPS) 70% and/or major comorbidities (renal/heart failure, grade ≥2 hearing loss) and/or previous allergic reactions to platinum compounds; 3= Platinum-sensitive but cumulative cisplatin dose received ≥225 mg/m² for locally-advanced disease. Pt are stratified according to: KPS (70% vs 80-100%); PD-L1 by Combined Positive Score (CPS ≥1 vs < 1); and HPV positivity (HPV+ oropharynx vs HPV-/non-oropharyngeal). 141 Pt are being randomized 2:1 to NIVOTAX (nivolumab 240 mg q2 weeks + weekly paclitaxel at 80 mg/m2 up to 12 weeks followed by maintenance nivolumab 480 mg/ q4 weeks) or ERBITAX ( weekly 250 mg/m2 plus paclitaxel 80 mg/m2 up to 12 weeks followed by maintenance cetuximab 250 mg/m2 weekly). Both arms will be continued up to a maximum of 24 months. Primary end-point is to evaluate treatment efficacy in terms of 2-year overall survival (2-y OS). It is assumed that 2-y OS in the NIVOTAX arm will be at least 26% (10% gain when compared to the expected 16% 2-y OS rate in this pt population). Secondary objectives include progression free survival (PFS), overall response rate, disease control rate, duration of response, 6m PFS, 5y-OS and safety profile. Response endpoints will be assessed using RECIST 1.1 criteria. As of February 12, 2021, 64 pts have been randomized. Planned safety data review for the first 10 pts treated with NIVOTAX regimen did not show any unexpected AE. Clinical trial information: NCT04282109.