NCT03544099

Pembrolizumab for Nasopharyngeal Carcinoma Patients With Detectable Plasma Epstein-Barr Virus DNA

Pembrolizumab for Nasopharyngeal Carcinoma Patients With Detectable Plasma Epstein-Barr Virus DNA But Without Clinically Detectable Residual Diseases and/or Metastases After Curative Chemoradiation - A Single Arm Phase II Trial

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: National Health Research Institutes, Taiwan · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm, multi-center, open-label, phase II trial to examine the efficacy of pembrolizumab for prolonging the one-year disease free survival in nasopharyngeal carcinoma patients with solely detectable EBV DNA after curative chemoradiation. Sixty-three patients will be enrolled in the trial.

Detailed description

This phase II study is aimed to prove the efficacy of adjuvant therapy with pembrolizumab for nasopharyngeal carcinoma patients with detectable plasma EBV DNA after curative chemoradiation. Nasopharyngeal cancer was a malignancy related to Epstein-Barr virus infection. It was a malignancy endemic in Southeast Asia, Taiwan, and China. The primary treatment was chemoradiation. The three-year disease free survival was around 50-60% for locally-advanced (stage IVA, IVB) NPC. Adjuvant chemotherapy after curative chemoradiation is a strategy to improve disease control rate for advanced NPC. However, two phase III trials in Taiwan (TCOG 1394) and China failed to prove its efficacy on improving disease control and overall survival. How to identify patients who are truly at risk is an important question for the therapy of advanced NPC. Plasma EBV DNA copy number is a biomarker predicting the recurrent risk of nasopharyngeal cancer. A higher level of plasma EBV DNA before chemoradiation is related to a poorer prognosis. A detectable EBV DNA after chemoradiation, which is a hint for occult residual or metastatic disease, is a strong predictor for early recurrence. The relapse free survival at two years for patients with detectable plasma EBV DNA (\> 0 copies/mL) was around 20%. The results of other similar trials are summarized on table 1. Cancer cells escaped from the immune surveillance by several mechanisms. One of them is activating immune inhibitory pathway by "immune checkpoints" . Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1) is one immune checkpoint axis to regulate immune response against cancer. Pembrolizumab (MK-3475), an anti-PD-1 antibody, had a good activity against melanoma and other types of cancers. The toxicity profiles were tolerable. In the Keynote-028 phase Ib trial, pembrolizumab showed good clinical activity against recurrent or metastatic NPC. The overall response rate is 22%, and the disease control rate is 77.8%. This data is encouraging for further clinical trials of pembrolizumab for NPC. PD-1/PD-L1 axis has an important role for the resistance of chemoradiation\[18\]. In patients refractory to chemoradiation, the expression of PD-1 and PD-L1 increased in the tumor. In animal model, sequential administration of anti-PD-1 after radiation significantly improved the progression free survival in mice with tumors \[19\]. This concept supports the investigator's sequential design for high-risk NPC patients.

Conditions

• Nasopharyngeal Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200mg Intravenous Solution

Timeline

• Start date: 2019-05-07
• Primary completion: 2021-12-31
• Completion: 2021-12-31
• First posted: 2018-06-01
• Last updated: 2023-04-11

Locations

8 sites across 1 country: Taiwan