459TiP - A single-arm, phase II study of envafolimab combined with chemoradiotherapy and recombinant human endostatin in high-risk locally advanced nasopharyngeal carcinoma

Background

About 20-30% of patients with locally advanced nasopharyngeal carcinoma (LA-NPC) still recur post-chemoradiotherapy, with distant metastasis dominating as the primary pattern of disease relapse. Immune checkpoint inhibitor was demonstrated to improve the 3-year event-free survival but not overall survival (OS) when used concurrently with chemoradiotherapy in LA-NPC, and exhibited potential synergistic anti-tumor effects when combined with anti-angiogenic therapy. Therefore, we aim to evaluate the efficacy and safety of sequential administration of PD-L1 inhibitor envafolimab combined with chemoradiotherapy and recombinant human endostatin in patients with high-risk LA-NPC.

Trial design

We conducted a multicenter, prospective, single-arm phase II clinical trial. Patients with newly diagnosed high-risk LA-NPC, i.e., T4N+ or N2-3 (8th AJCC/UICC staging), or pretreatment EBV-DNA ≥4000 copies/ml, or grade 3 image-identified lymph node extranodal extension are eligible. This trial plans to enroll 45 patients. In induction treatment phase, all participants will receive subcutaneous injection of envafolimab on day 1 at 300 mg and intravenous continuous infusion of endostar for 72h at 210 mg, in combination with gemcitabine (on days 1 and 8 at 1 g/m²) plus cisplatin (on day 1 at 80 mg/m²), administered every 3 weeks for 3 cycles, plus concurrent intensity-modulated radiotherapy (69.96Gy/33fractions/7weeks,5 fractions/week) with cisplatin at a dose of 100mg/m² every 3 weeks for 2 cycles, followed by adjuvant envafolimab every 3 weeks for 8 cycles. The study drug will be discontinued if there were unacceptable toxic effects, confirmed disease recurrence (either by histology or imaging), withdrawal of consent, or fulfilment of a criterion for discontinuation. The primary endpoint is 3-year progress free survival (PFS) per RECIST 1.1 criteria. The secondary objectives are 3-year OS, 3-year locoregional relapse free survival (LRRFS), 3-year distant metastases free survival (DMFS), incidence rate of adverse events (AEs) and compliance. As of July 2024, 18% of the planned 45 subjects have been enrolled.

Clinical trial identification

NCT06059261.

Legal entity responsible for the study

Chongqing University Cancer Hospital.

Funding

Zhongguancun Precision Medicine Foundation.

Disclosure

All authors have declared no conflicts of interest.