Compassionate Use of Asparaginase and Pembrolizumab Combination Theaapy for Nasopharyngeal Carcinoma

Compassionate Use of Combination Therapy with Asparaginase and Pembrolizumab in Patients with Nasopharyngeal Carcinoma

The goal of this study is to investigate the outcomes of patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) or recurrent-metastatic nasopharyngeal carcinoma (RM-NPC) treated with a combination of immune checkpoint blockade (ICB) and asparaginase.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma (NPC)
• Intervention / Treatment: Drug: Anti-PD1; Drug: asparaginase

Detailed Description

This study is being conducted to investigate the synergistic effect of combining asparaginase with immune checkpoint blockade (ICB) in tumor-bearing mice. Findings indicate that asparaginase enhances CD8+ T cell activation, and previous reports have shown that nasopharyngeal carcinoma (NPC) patients exhibit a lower response rate to ICB treatment. This study aims to determine whether the combination therapy of asparaginase and ICB is more effective or less effective compared to the standard ICB-only approach for patients with locoregionally advanced (LA-NPC) or recurrent-metastatic NPC (RM-NPC). Participants are being enrolled who have previously received ICB but continue to experience disease progression.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Patients who have previously received immune checkpoint blockade therapy but are still experiencing disease progression -

Exclusion Criteria: Active autoimmune disease

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination therapy; The patients will receive asparaginase 10000IU/vail IM QD for three or five days, followed by pembrolizumab treatment. and Pembrolizumab 100mg in normal saline 100ml infusion over 30 minutes.	Drug: Anti-PD1; Pembrolizumab 100mg in normal saline 100ml infusion over 30 minutes for every two month; Drug: asparaginase; The patients will receive asparaginase 10000IU/vail IM QD for three or five days.
Placebo Comparator: anti-PD1 alone; The patients will receive pembrolizumab treatment.	Drug: Anti-PD1; Pembrolizumab 100mg in normal saline 100ml infusion over 30 minutes for every two month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Analysis of Plasma EBV DNA Levels for Treatment Response	In nasopharyngeal carcinoma (NPC), plasma Epstein-Barr virus (EBV) DNA serves as a crucial biomarker for both diagnosis and monitoring. EBV, a herpesvirus that infects epithelial cells, is strongly associated with NPC development, especially in endemic regions. The transformation from latent EBV infection to active viral replication is considered a critical step in NPC pathogenesis. This transformation can be detected through circulating viral DNA levels in plasma or by measuring antibodies against various EBV antigens, such as EBNA1, VCA, and EA-D. Elevated EBV DNA levels often correlate with tumor burden and may serve as a predictor of NPC recurrence or progression. Consequently, plasma EBV DNA testing has become an essential tool in NPC clinical management, helping to guide treatment decisions and evaluate treatment response.	Until the end of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FDG PET/CT scan	FDG PET/CT for detecting tumor existence	3 month

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Study Chair: Huang-Yu Yang, M.D./Ph.D, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Gnanaprakasam JNR, Kushwaha B, Liu L, Chen X, Kang S, Wang T, Cassel TA, Adams CM, Higashi RM, Scott DA, Xin G, Li Z, Yang J, Lane AN, Fan TW, Zhang J, Wang R. Asparagine restriction enhances CD8+ T cell metabolic fitness and antitumoral functionality through an NRF2-dependent stress response. Nat Metab. 2023 Aug;5(8):1423-1439. doi: 10.1038/s42255-023-00856-1. Epub 2023 Aug 7.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: NPC; asparaginase; ICB
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma; Antineoplastic Agents; Asparaginase
• Other Study ID Numbers: IRB NO. 202400085B0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No