Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial

Yijun Hua, Rui You, Zhiqiang Wang, Peiyu Huang, Mei Lin, Yanfeng Ouyang, Yulong Xie, Xiong Zou, Youping Liu, Chongyang Duan, Yonglong Liu, Chenmei Gu, Rongzeng Liu, Qi Yang, Rou Jiang, Mengxia Zhang, Xi Ding, Siyuan Chen, Chao Lin, Rui Sun, Mingyuan Chen, Yijun Hua, Rui You, Zhiqiang Wang, Peiyu Huang, Mei Lin, Yanfeng Ouyang, Yulong Xie, Xiong Zou, Youping Liu, Chongyang Duan, Yonglong Liu, Chenmei Gu, Rongzeng Liu, Qi Yang, Rou Jiang, Mengxia Zhang, Xi Ding, Siyuan Chen, Chao Lin, Rui Sun, Mingyuan Chen

Abstract

Background: Toripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1. We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC).

Methods: We conducted a single-arm, phase II trial with patients with rNPC who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate at 3 months post radiotherapy. The secondary endpoints included safety profiles, progression-free survival (PFS).

Results: Between May 2019 and January 2020, a total of 25 patients with rNPC were enrolled (18 men (72.0%) and 7 women (28.0%); median (IQR) age, 49.0 (43.5-52.5) years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month PFS was 91.8% (95% CI 91.7% to 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine kinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively.

Conclusions: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in patients with rNPC.

Trial registration number: NCT03854838.

Keywords: clinical trials; head and neck neoplasms; immunotherapy; phase II as topic; radiotherapy.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Trial profile. RECIST, Response Evaluation Criteria in Solid Tumors. AJCC, American Joint Committee on Cancer.
Figure 2
Figure 2
Antitumor activity. (A) Change in individual tumor burden during the first 12 months after the completion of radiotherapy from baseline assessed by Investigators per RECIST V.1.1 (N=25); (B) maximal change in tumor size from baseline assessed by investigators per RECIST V.1.1 (N=25). The length of the bar represents the maximal decrease or minimal increase in target lesions. RECIST, Response Evaluation Criteria in Solid Tumors.
Figure 3
Figure 3
Kaplan-Meier curves of the progression-free survival. Progression-free survival was assessed in the whole population (n=25).

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