247TiP - Addition of induction, concurrent and maintenance durvalumab to induction and concurrent chemoradiation vs induction and concurrent chemoradiation for previously untreated locoregionally advanced nasopharyngeal carcinoma: A phase II randomised-controlled trial

Background

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Despite the most aggressive and devastating treatment with induction chemotherapy followed by concurrent chemoradiation, about 20-30% of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) suffer from relapse at 5 years. Addition of anti-PD(L)1 immune checkpoint inhibitor to this intensive radical treatment may help improve treatment outcomes and survival. We are conducting a phase II randomised-controlled trial on adding durvalumab as induction, concurrent and maintenance therapy to induction and concurrent chemoradiation compared to the same regimen without durvalumab for previously untreated LANPC patients.

Trial design

Patients with previously untreated LANPC (stage III to IVA disease except T3N0M0 based on TNM-8) are screened for study eligibility. After fulfilling all the study criteria, they will be randomised (in 1:1 ratio) to (a) experimental arm with a fixed dose durvalumab 1500mg intravenously administered every 4 weeks for 13 cycles and 3 cycles of induction chemotherapy with gemcitabine (1000mg/m2 on day 1 and day 8) and cisplatin (100mg/m² on day 1) every 3 weeks followed by concurrent chemoradiation with 3-weekly cisplatin (100mg/m²) infusion, or (b) control arm with the same regimen of induction chemotherapy and concurrent chemoradiation. The primary study end point is progression-free survival while the secondary end points are objective response, overall survival, safety profiles, change in tumour microenvironment before and after induction chemotherapy and concurrent chemoradiation (with or without durvalumab), and change in PD-L1 positive circulating tumour cells before and after induction chemotherapy and concurrent chemoradiation (with or without durvalumab). The study is still ongoing and expected to complete patient accrual (n=118) in end of December 2022.

Clinical trial identification

NCT04447612. Release date: 25 June 2020.

Legal entity responsible for the study

Department of Clinical Oncology, LKS Faculty of Medicine, The University of Hong Kong.

Funding

AstraZeneca.

Disclosure

V.H.F. Lee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Amgen, Takeda, Bristol Myers Squibb, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Boston Scientific, Novartis, Merck Pharmaceuticals. All other authors have declared no conflicts of interest.