Neoadjuvant and Adjuvant Tislelizumab for Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

A Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Tislelizumab + Chemotherapy Followed by Adjuvant Tislelizumab for the Treatment of Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05211232
• Other study ID #: 2021-FXY-452
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 10, 2022
• Est. completion date: May 30, 2028

Study information

• Verified date: April 2024
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and tislelizumab in neoadjuvant therapy combined with tislelizumab in adjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

Description:

Platinum-based concurrent chemoradiotherapy 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. The results of GP combined with concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma showed 10% of locoregionally advanced NPC patients had complete response after three cycles of GP neoadjuvant chemotherapy, 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 chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based neoadjuvant chemotherapy 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 the treatment of tumor 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. The current NCCN guidelines recommend anti PD-1 monoclonal antibody as a second-line treatment for recurrent or metastatic NPC. More and more evidence show that immunotherapy combined with chemotherapy has a synergistic effect in treating tumors. GP chemotherapy combined with anti PD-1 antibody has achieved the initial effect in NPC. Phase 1 trials have shown the combination of camrelizumab plus GP chemotherapy in recurrent or metastatic NPC led to a proportion of 91% patients achieving an objective response. In addition, previous studeis showed that PD-1 antibody adjuvant therapy had good feasibility and effectiveness in the treatment of nasopharyngeal carcinoma. Tislelizumab, approved by the National Medical Products Administration in China, is an anti-PD-1 monoclonal IgG4 antibody with higher affinity to PD-1 than pembrolizumab and nivolumab and was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Multiple clinical trials have shown strong anti-neoplastic activity of tislelizumab in various tumors including NPC. Clinical trial has shown an objective response rates of 43% in patients with recurrent metastatic nasopharyngeal carcinoma treated with tirelizumab, which is superior to other anti PD-1 monoclonal antibodys. So we hypothesize that GP neoadjuvant chemotherapy combined with tislelizumab and tislelizumab adjuvant therapy could further improve survival of patients with locaregionally advanced NPC. Based on this, this study aims to evaluate the efficacy and safety of gemcitabine plus cisplatin chemotherapy combined with tislelizumab neoadjuvant therapy, followed by cisplatin based concurrent chemoradiotherapy, then followed by tislelizumab adjuvant therapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for individualized comprehensive treatment in NPC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: May 30, 2028
• Est. primary completion date: May 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients must be informed of the investigational nature of this study and give written informed consent.

2. Age = 18 years and =70 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 III-IVA (AJCC 8th, except T3N0,T3N1(Only retropharyngeal lymph nodes metastasized).

5. No previous anti-tumor treatment.

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 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) and aspartate aminotransferase (AST) =2×upper limit of normal (ULN),serum total bilirubin (TBIL) =2.0 times the upper limit of normal (ULN) .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.

17. Patients with positive HCV antibody test will only be enrolled in this study if the PCR test for HCV RNA is negative.

18. Patients who were known to be intolerable or allergic to treatment drug.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Tislelizumab
GP combine with Tislelizumab neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy
• Placebo
GP combine with Placebo neoadjuvant therapy+CCRT+Tislelizumab adjuvant therapy

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	Guizhou Cancer Hospital	Guiyang	Guizhou
China	Wuzhou Red Cross Hospital	Wuzhou	Guangxi
China	The Affiliated Hospital of Guangdong Medical College	Zhanjiang	Guangdong

Sponsors (5)

Lead Sponsor	Collaborator
Sun Yat-sen University	Affiliated Hospital of Guangdong Medical University, Cancer Hospital of Guizhou Province, Hunan Cancer Hospital, Wuzhou Red Cross Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Y — View Citation

Shen L, Guo J, Zhang Q, Pan H, Yuan Y, Bai Y, Liu T, Zhou Q, Zhao J, Shu Y, Huang X, Wang S, Wang J, Zhou A, Ye D, Sun T, Gao Y, Yang S, Wang Z, Li J, Wu YL. Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phas — View Citation

Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2020 Sep 1;26(17): — View Citation

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response	CR assessed by investigator, according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the neoadjuvant therapy. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) .	9 weeks
Primary	Progression-free Survival (PFS)	defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.	3 years
Secondary	Overall Survival(OS)	defined as the time from random assignment to death from any cause or censored at the date of last follow-up.	3 years
Secondary	Locoregional failure-free survival(LRRFS)	defined as the time from random assignment to local or regional relapse, or death from any cause.	3 years
Secondary	Distant metastasis-free survival(DMFS)	defined as the time from random assignment to distant metastasis, or death from any cause.	3 years
Secondary	Number of participants with adverse events	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 3 years