GP Plus Adebrelimab Versus GP Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma

GP Plus Adebrelimab Versus GP Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma

The purpose of this study is to explore the efficacy and safety of neoadjuvant GP chemotherapy plus adebrelimab versus neoadjuvant GP chemotherapy in treating high-risk locoregionally advanced nasopharyngeal carcinoma patients.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: GP; Drug: Adebrelimab; Drug: concurrent chemoradiotherapy (CCRT)

Detailed Description

Platinum-based neoadjuvant chemotherapy plus concurrent chemoradiotherapy (CCRT) is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Gemcitabine plus cisplatin(GP) has been demonstrated an effective chemotherapy regimen for NPC patients in previous studies. Three cycles of GP neoadjuvant chemotherapy resulted in 10% of complete response rate, and GP neoadjuvant chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as compared with concurrent chemoradiotherapy alone. Therefore, GP has been established as the highest level of evidence-based neoadjuvant chemotherapy regimen in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Recently, immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) monoclonal antibody has shown promising efficacy in NPC patients. Clinical trials have shown objective response rates of 20.5%-34% in patients with recurrent or metastatic NPC patients receiving anti PD-1 monoclonal antibody immunotherapy including pembrolizumab, nivolumab, camrelizumab, and toripalimab. GP chemotherapy combined with anti PD-1 antibody were hence considered in treating locoregionally advanced NPC. Concurrent radiotherapy might cause T-cell dysfunction, and larger-volume elective nodal irradiation might hinder immunotherapy effects by directly depleting memory T cells. No survival benefit was observed when PD-1 blockade was added concurrently to the CCRT phase for treating head and neck cancers. On the contrary, several studies have demonstrated that administration of immunotherapy in the neoadjuvant setting modified the primary tumor into an antigen source for T-cell expansion and priming, thereby resulting in stronger effects than those of adjuvant therapy. Currently there were 3 trials exploring the addition of immunotherapy to chemoradiotherapy, the preliminary results of which were recently published. These trials had different trial designs, with two trials utilized anti PD-1 inhibitors in all treatment phases including neoadjuvant, concurrent and adjuvant phases, The third trial, which was conducted by our team, gave anti PD-1 inhibitor only in the neoadjuvant phase, and promising efficacy was observed in our study.

Adebrelimab is a recombinant humanized IgG4 monoclonal antibody with specificity for PD-L1. In a phase III clinical trial of extensive stage small-cell lung cancer, the addition of adebrelimab significantly improved the median overall survival compared with the control group (15.3 vs. 12.8，HR 0.72, P=0.0017). So we hypothesize that GP neoadjuvant chemotherapy combined with adebrelimab could further improve the survival of patients with high-risk locoregionally advanced NPC (diagnosed with T4 or N2-3 disease). Therefore, we designed this phase II multi-center randomized controlled trial to evaluate whether GP neoadjuvant chemotherapy combined with adebrelimab plus cisplatin-based CCRT improve the complete response rate of high-risk locoregionally advanced NPC patients compared with GP neoadjuvant chemotherapy plus CCRT.

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hai-Qiang Mai, MD, PhD; Phone Number: 8613570027338; Email: maihq@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Not yet recruiting
    • Zhujiang Hospital of Southern Medical University
    • Contact: Junguo Bu
  • Guangzhou, China
    • Not yet recruiting
    • Affiliated Cancer Hospital and institute of Guangzhou Medical University
    • Contact: Bin Qi
  • Guangzhou, China
    • Not yet recruiting
    • Sun Yat-Sen Memorial Hospital
    • Contact: Xingsheng Qiu
  • Guangzhou, China
    • Not yet recruiting
    • The Affiliated Panyu Central Hospital of Guangzhou Medical University
    • Contact: Guorong Zou
  • Liuzhou, China
    • Not yet recruiting
    • Liuzhou Workers Hospital
    • Contact: Ying Lu
  • Nanning, China
    • Not yet recruiting
    • Guangxi Medical University Affiliated Cancer Hospital
    • Contact: Ling Li
  • Shantou, China
    • Not yet recruiting
    • Cancer Hospital of Shantou University Medical College
    • Contact: Chuangzhen Chen
  • Shenzhen, China
    • Recruiting
    • The Second People's Hospital of Shenzhen
    • Contact: Beiping Miao
  • Shenzhen, China
    • Not yet recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences, ShenZhen center
    • Contact: Jianggu Zhang
  • Shenzhen, China
    • Not yet recruiting
    • The university of Hongkong - Shenzhen hospital
    • Contact: Jishi Li
  • Zhangjiang, China
    • Not yet recruiting
    • Guangdong Medical School First Affiliated Hospital
    • Contact: Danxian Jiang
  • Guangdong
    • Foshan, Guangdong, China
      • Not yet recruiting
      • Foshan First People's Hospital
      • Contact: Ning Zhang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients must be informed of the investigational nature of this study and give written informed consent.
2. Age ≥ 18 years and ≤65 years, men or non-pregnant women.
3. Patients with histologically confirmed Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type, WHO II or III).
4. Tumor staged as T4N0-1M0 or T1-4N2-3M0 (AJCC 8th).
5. No previous anti-tumor treatment.
6. Eastern Cooperative Oncology Group (ECOG) score 0 or 1.
7. Adequate marrow function: White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL) ≤2×upper limit of normal (ULN).
9. Adequate renal function: creatinine clearance rate ≥ 60 ml/min or Creatinine ≤ 1.5× upper limit of normal value.

Exclusion Criteria:

1. Patients with recurrent or metastatic nasopharyngeal carcinoma.
2. Histologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
3. Prior therapy with radiation or systemic chemotherapy.
4. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
5. Seropositivity for human immunodeficiency virus (HIV).
6. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
7. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti- PD-L1, anti-CTLA-4 antibodies.
8. Patients with immunodeficiency disease or a history of organ transplantation.
9. Received large doses of glucocorticoids, anticancer monoclonal antibodies, or other immunosuppressants within 4 weeks.
10. Patients with severe dysfunction of heart, liver, lung, kidney or marrow.
11. Patients with severe, uncontrolled disease or infections.
12. Received other research drugs or in other clinical trials at the same time.
13. Refuse or fail to sign the informed consent .
14. Patients with other treatment contraindications.
15. Patients with personality or mental disorders, incapacity or limited capacity for civil conduct.
16. Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV deoxyribonucleic acid (HBV DNA) ≥1000cps/ml or 200 IU/ml.
17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GP neoadjuvant therapy+CCRT; Patients receive neoadjuvant therapy with gemcitabine (1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT).	Drug: GP; gemcitabine + cisplatin; Drug: concurrent chemoradiotherapy (CCRT); concurrent chemoradiotherapy (CCRT)
Experimental: GP combined with adebrelimab neoadjuvant therapy+CCRT; Adebrelimab (1200mg) to be administered on Day 1 of the Lead-in Phase (-14 days to the start of the neoadjuvant chemoimmunotherapy phase). Patients receive neoadjuvant therapy with gemcitabine (1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and adebrelimab (given 1200mg on day 1) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1, D22, D43 of RT).	Drug: GP; gemcitabine + cisplatin; Drug: Adebrelimab; a PD-L1 inhibitor; Drug: concurrent chemoradiotherapy (CCRT); concurrent chemoradiotherapy (CCRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR) rate	The proportion of patients who achieve complete response after neoadjuvant chemotherapy or chemoimmunotherapy as assessed by RECIST 1.1.	11weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival(EFS)	defined as the time from randomisation to documented locoregional relapse /distant metastasis or death due to any cause, whichever occurred first.	2 years
Overall survival (OS)	defined as the time from randomisation to death due to any cause.	2 years
Locoregional relapse-free survival（LRRFS）	defined as the time from randomisation to documented locoregional relapse or death due to any cause.	2 years
Distant metastasis-free survival (DMFS)	defined as the time from randomisation to documented distant metastasis or death due to any cause	2 years
Toxicity profiles	Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.	Up to 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2028

Study Registration Dates

• First Submitted: June 6, 2024
• First Submitted That Met QC Criteria: June 11, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: 2024-FXY-154

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No