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

NCT ID: NCT05587374

Last Updated: 2025-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

490 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-01

Study Completion Date

2029-08-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Nasopharyngeal Carcinoma Nasopharyngeal Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open-label

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cadonilimab arm

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.

Group Type EXPERIMENTAL

Cadonilimab

Intervention Type 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.

Gemcitabine

Intervention Type DRUG

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

Cisplatin

Intervention Type 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

Intensity-modulated radiotherapy

Intervention Type RADIATION

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

Chemoradiation arm

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.

Group Type ACTIVE_COMPARATOR

Gemcitabine

Intervention Type DRUG

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

Cisplatin

Intervention Type 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

Intensity-modulated radiotherapy

Intervention Type RADIATION

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Gemcitabine

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

Intervention Type DRUG

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

Intervention Type DRUG

Intensity-modulated radiotherapy

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

Intervention Type RADIATION

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

PD-1/CTLA-4 bi-specific antibody GEM DDP IMRT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Akeso Pharmaceuticals, Inc.

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jun Ma, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jun Ma, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Site Status

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

Hefei, Anhui, China

Site Status

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status

Dongguan Peaple's Hospital

Dongguan, Guangdong, China

Site Status

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Zhongshan city Peaple's Hospital

Zhongshan, Guangdong, China

Site Status

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Site Status

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Site Status

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

Site Status

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

Wuhan, Hubei, China

Site Status

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

Wuhan, Hubei, China

Site Status

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status

Shandong Province Cancer Hospital

Jinan, Shandong, China

Site Status

Changhai Hospital of Shanghai

Shanghai, Shanghai Municipality, China

Site Status

Countries

Review the countries where the study has at least one active or historical site.

China

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 31150573 (View on PubMed)

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

Reference Type RESULT
PMID: 35986837 (View on PubMed)

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.

Reference Type RESULT
PMID: 28837405 (View on PubMed)

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.

Reference Type RESULT
PMID: 29584545 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

AK104-IIT-019

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.