942TiP - A randomized controlled clinical trial of neoadjuvant immunochemotherapy vs up-front surgery in patients with locally advanced resectable oral squamous cell carcinoma (Tophill trial)

Background

Neoadjuvant therapy (NAT) is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of NAT for patients with locally advanced oral squamous cell carcinoma (LA-OSCC). Early clinical investigations suggest that the pathological efficacy of neoadjuvant immunochemotherapy (NAICT) is superior to neoadjuvant immunotargeted therapy, neoadjuvant chemotargeted therapy, or neoadjuvant chemotherapy. And in the single-arm NAICT clinical trial (NCT04473716), the results showed that the NAICT regimen was well tolerated, with a major pathological response (MPR) rate of 60% and 2-year overall survival (OS) of 90%, which were better than previously reported patients receiving standard treatment for LA-OSCC. These results have supported the conduction of a randomized controlled trials with larger sample size. The aim of present trial is to evaluate the prognostic efficacy of 2-year survival rate in patients with LA-OSCC receiving NAICT with tislelizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy compared with standard therapy.

Trial design

Tophill Trial is a prospective, multicenter, randomized controlled trial. 134 eligible patients, who are 18-75 years of age with clinical stage III-IVA (AJCC 8^th) LA-OSCC and ECOG PS 0–1, will be randomized 1:1 to receive NAICT (2 cycles, albumin paclitaxel 260 mg/m^2, cisplatin 75mg/m² plus tislelizumab 200 mg D1 Q3W) plus radical surgery and postoperative adjuvant treatment (experimental group) or the standard treatment regimen (up-front surgery plus postoperative adjuvant treatment) (control group). The primary objective is to investigate whether NAICT can improve the 2-year event-free survival (EFS) and OS of patients with LA-OSCC. The second objective is to investigate whether neoadjuvant immunochemotherapy can improve the 2-year disease-free survival (DFS) and the rate of MPR.

Clinical trial identification

Enrollment began in April, 2024. NCT06258811.

Editorial acknowledgement

Legal entity responsible for the study

Huashan Hospital, Fudan University.

Funding

Beigene Ltd; Qilu pharmaceutical.

Disclosure

All authors have declared no conflicts of interest.