Cadonilimab (PD-1/CTLA-4 Bi-specific Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Cadonilimab (PD-1/CTLA-4 Bi-specific Antibody) Combined With Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma: a Randomized, Controlled, Multicenter, Phase 3 Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05587374
• Other study ID #: AK104-IIT-019
• Status: Recruiting
• Phase: Phase 3
• Start date: August 1, 2023
• Est. completion date: January 1, 2027

Study information

• Verified date: November 2023
• Source: Sun Yat-sen University
• Contact: Jun Ma, M.D.
• Phone: +862087343469
• Email: majun2[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial aimed to compare cadonilimab combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in high-risk locoregionally-advanced nasopharyngeal carcinoma (LANPC).

Description:

The trial plans to enroll patients with stage III-IVA (AJCC 8th, except T3N0-1 or T4N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus cadonilimab in induction chemotherapy and adjuvant chemotherapy. All patients will receive intensity-modulated radiotherapy (IMRT). Cadonilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 14 cycles in adjuvant therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 418
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients with histologically confirmed nasopharyngeal carcinoma.

2. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).

3. Eastern Cooperative Oncology Group performance status =1.

4. Adequate marrow function: neutrocyte count=1.5×10e9/L, hemoglobin =90g/L and platelet count =100×10e9/L.

5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) =2.5×upper limit of normal (ULN), and bilirubin = 1.5×ULN.

6. Adequate renal function: creatinine clearance rate = 60 ml/min (Cockcroft-Gault formula).

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

8. Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug

Exclusion Criteria:

1. Age > 65 or < 18.

2. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml

3. Hepatitis C virus (HCV) antibody positive

4. Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).

5. Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone =10mg/d, inhale or topical corticosteroid will be allowed.

6. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.

7. Has a known history of interstitial lung disease.

8. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.

9. Is pregnant or breastfeeding.

10. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.

11. Has known allergy to large molecule protein products or any compound of cadonilimab.

12. Has a known history of human immunodeficiency virus (HIV) infection.

13. Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Cancer
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Cadonilimab
Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
• Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
• Cisplatin
Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

Radiation:
• Intensity-modulated radiotherapy
Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

Locations

Country	Name	City	State
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Hunan Cancer Hospital	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Dongguan Peaple's Hospital	Dongguan	Guangdong
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Sun Yat-sen Memorial Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Cancer Hospital of Guizhou Medical University	Guiyang	Guizhou
China	The First Affiliated Hospital of University of Science and Technology of China	Hefei	Anhui
China	Cancer Hospital of Guangxi Medical University	Nanning	Guangxi
China	Changhai Hospital of Shanghai	Shanghai	Shanghai
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Hubei Province Cancer Hosiptal	Wuhan	Hubei
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Zhongshan city Peaple's Hospital	Zhongshan	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Akeso Pharmaceuticals, Inc.

Country where clinical trial is conducted

China, 

References & Publications (4)

Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharynge — View Citation

Keam SJ. Cadonilimab: First Approval. Drugs. 2022 Aug;82(12):1333-1339. doi: 10.1007/s40265-022-01761-9. — View Citation

Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Ac — 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	Failure-free survival (FFS)	calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.	3 years
Secondary	Overall survival (OS)	calculated from randomization to the date of death from any cause.	3 years
Secondary	Distant metastasis-free survival (DMFS)	calculated from randomization to the date of first distant metastasis.	3 years
Secondary	Locoregional recurrence-free survival (LRRFS)	calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.	3 years
Secondary	Adverse events (AEs) and serious adverse events (SAEs)	Graded according to CTCAE V5.0.	3 years
Secondary	Quality of life (QoL)	The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30)version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.	3 years
Secondary	Failure-free survival (FFS) within different subgroups	analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (=4000copies/ml vs. >4000copies/ml), different PD-L1 expression levels, age, gender, performance status, T category, N category, and stage (III vs. IVA).	3 years