Cadonilimab (PD-1/CTLA-4 Bispecific Blockade) and Chemoradiotherapy in Nasopharyngeal Carcinoma (GEMSTONE)

NCT05587374 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: AK104-IIT-019
• Study Type: interventional
• Target: 490
• Locations: 1 country
• Sites: 18

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).

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Cancer

Keywords

immunotherapy; PD-1/CTLA-4 Bi-specific Antibody; Chemoradiotherapy

Outcome Measures

Primary Outcomes (2)

• Failure-free survival (FFS) in intention-to-treat population

  multiple endpoint 1: calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.

  3 years

• Overall survival (OS) in intention-to-treat population

  multiple endpoint 2: calculated from randomization to the date of death from any cause.

  3 years

Secondary Outcomes (8)

• Failure-free survival (FFS) in per-protocol population

  3 years

• Overall survival (OS) in per-protocol population

  3 years

• Locoregional recurrence-free survival (LRRFS)

  3 years

• Distant metastasis-free survival (DMFS)

  3 years

• Adverse events (AEs) and serious adverse events (SAEs)

  3 years

Other Outcomes (3)

• Correlation between pre-treatment PD-L1 expression level and FFS

  3 years

• Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level

  3 years

• Evaluate failure-free survival in the subgroup of clinical stage

  3 years

Study Arms (2)

Cadonilimab arm

EXPERIMENTAL

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. 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.

Drug: Cadonilimab; Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

Chemoradiation arm

ACTIVE COMPARATOR

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.

Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

Interventions

Cadonilimab DRUG

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.

Also known as: PD-1/CTLA-4 bi-specific antibody

Cadonilimab arm

Gemcitabine DRUG

Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.

Also known as: GEM

Cadonilimab arm; Chemoradiation arm

Cisplatin DRUG

Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

Also known as: DDP

Cadonilimab arm; Chemoradiation arm

Intensity-modulated radiotherapy RADIATION

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

Also known as: IMRT

Cadonilimab arm; Chemoradiation arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed nasopharyngeal carcinoma.
• Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
• Eastern Cooperative Oncology Group performance status ≤1.
• Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
• Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
• Patients must be informed of the investigational nature of this study and give written informed consent.
• 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

You may not qualify if:

• Age \> 65 or \< 18.
• Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA \>1×10e3 copies/ml or 200IU/ml
• Hepatitis C virus (HCV) antibody positive
• 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).
• 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.
• 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.
• Has a known history of interstitial lung disease.
• Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
• Is pregnant or breastfeeding.
• Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
• Has known allergy to large molecule protein products or any compound of cadonilimab.
• Has a known history of human immunodeficiency virus (HIV) infection.
• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (18)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233000, China

Location

The First Affiliated Hospital of University of Science and Technology of China

Hefei, Anhui, 230041, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, China

Location

Dongguan Peaple's Hospital

Dongguan, Guangdong, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Zhongshan city Peaple's Hospital

Zhongshan, Guangdong, China

Location

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

Location

Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

Shandong Province Cancer Hospital

Jinan, Shandong, China

Location

Changhai Hospital of Shanghai

Shanghai, Shanghai Municipality, China

Location

Related Publications (4)

• 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.

  PMID: 31150573 RESULT

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

  PMID: 35986837 RESULT

• 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 Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.

  PMID: 28837405 RESULT

• 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.

  PMID: 29584545 RESULT

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Interventions

Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Jun Ma, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 20, 2022
• Study Start: August 1, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)