A phase II exploratory study of stratified therapy using toripalimab plus GP induction followed by concurrent immunoradiotherapy for locally advanced nasopharyngeal carcinoma.

Abstract

e18070 Background: Immunotherapy is under extensive investigation for the treatment of locally advanced nasopharyngeal carcinoma (LANPC). The decreased tumor burden of induction immunotherapy may reduce the reliance on platinum-based chemotherapy and its associated toxicity during the concurrent phase. Therefore, this study explored response-adaptive therapy according to response of induction immunochemotherapy. Methods: This phase II study enrolled 30 patients with World Health Organization type II/III, stage III-IVA NPC. In the induction phase (Phase 1), patients received two cycles of toripalimab (240 mg, D1 Q3W) plus the GP regimen (gemcitabine 1000 mg/m² D1, 8, and cisplatin 80 mg/m² D1, Q3W), followed by efficacy assessment. Patients with disease progression (PD) proceeded directly to Phase 2. Other patients received two additional induction cycles. Prior to Phase 2, patients were stratified based on treatment response: 1)patients achieving partial response (PR) with ≥50% tumor reduction or a complete response (CR) received toripalimab concurrently with intensity-modulated radiotherapy (IMRT) for three cycles; 2) patients with PR <50%, stable disease (SD), or PD received concurrent IMRT with cisplatin and toripalimab. Results: Between October 2024 and December 2025, 30 patients were enrolled. One patient discontinued treatment after two cycles due to grade 3 immune-related keratitis. As of January 19th 2026, 29 patients completed therapy of Phase 1, 23 patients also completed the subsequent phase. All 29 patients completed four cycles induction therapy without PD. The overall objective response rate (ORR) was 89.66%, with 10 cases (34.48%) of CR, 16 cases (55.17%) of PR, and 3 cases (10.34%) of SD. Among PR patients, 12 (41.38% of total) achieved a tumor reduction of ≥50%. In safety analysis, 8 patients (26.67%) experienced grade 3-4 chemotherapy-related adverse events, most commonly anemia (10.00%), followed by nausea, vomiting, thrombocytopenia, and neutropenia (3.33% respectively). 1 patient (3.33%) developed a grade 3 immune-mediated adverse event (irAE) (keratitis). No grade 4 irAE was reported. Conclusions: Induction therapy with toripalimab combined with the GP regimen demonstrates a high tumor response rate and a manageable safety profile in patients with LANPC. These findings support the rationale for de-escalating platinum-based chemotherapy in subsequent concurrent treatment phases to potentially reduce toxicity. Clinical trial information: ChiCTR2400089302.