Clinical trial NCT05587374: Cadonilimab (PD-1/CTLA-4 Bispecific Blockade) and Chemoradiotherapy in Nasopharyngeal Carcinoma (GEMSTONE)
Official title: Cadonilimab as Induction-adjuvant PD-1/CTLA-4 Bispecific Blockade Combined With Induction Chenotherapy and Concurrent Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma: a Multicenter, Randomized, Controlled, Multicenter, Phase 3 Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Nasopharyngeal Cancer
Keywords: immunotherapy
PD-1/CTLA-4 Bi-specific Antibody
Chemoradiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Akeso Pharmaceuticals, Inc.
First posted: 2022-10-20
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: The trial plans to enroll patients with non-metastatic stage III-IVA (AJCC 8th, T4N1 or T1-4N2-3) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine-cisplatin induction chemotherapy and concurrent chemoradiotherapy (standard-therapy group) or cadonilimab combined with standard therapy (cadonilimab group). Cadonilimab was administered at a dosage of 10 mg per square meter intravenously once every 3 weeks for up to 17 cycles (3 induction cycles and 14 adjuvant cycles).

Eligibility criteria: 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.

Primary outcomes:
measure: Failure-free survival (FFS) in intention-to-treat population
timeFrame: 3 years
measure: Overall survival (OS) in intention-to-treat population
timeFrame: 3 years
Secondary outcomes:
measure: Failure-free survival (FFS) in per-protocol population
timeFrame: 3 years
measure: Overall survival (OS) in per-protocol population
timeFrame: 3 years
measure: Locoregional recurrence-free survival (LRRFS)
timeFrame: 3 years
measure: Distant metastasis-free survival (DMFS)
timeFrame: 3 years
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 3 years
measure: Quality of life (QoL)
timeFrame: week 1, 20, 40, 64
measure: Failure-free survival (FFS) within different subgroups
timeFrame: 3 years
measure: Tumor response
timeFrame: Through study completion, an average of 1.2 year
Other outcomes:
measure: Correlation between pre-treatment PD-L1 expression level and FFS
timeFrame: 3 years
measure: Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level
timeFrame: 3 years
measure: Evaluate failure-free survival in the subgroup of clinical stage
timeFrame: 3 years
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Dongguan
country: China
facility: Dongguan Peaple's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan city Peaple's Hospital
state: Guangdong
city: Nanning
country: China
facility: Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Province Cancer Hosiptal
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Jinan
country: China
facility: Shandong Province Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
Study officials:
affiliation: Sun Yat-sen University
name: Jun Ma, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
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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 Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.