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

January 20, 2025 updated by: Jun Ma, MD, Sun Yat-sen University

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

490

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Anhui
      • Bengbu, Anhui, China, 233000
        • The first affiliated hospital of bengbu medical college
      • Hefei, Anhui, China, 230041
        • The First Affiliated Hospital of University of Science and Technology of China
    • Beijing
      • Beijing, Beijing, China
        • Cancer Hospital Chinese Academy of Medical Sciences
    • Fujian
      • Fuzhou, Fujian, China
        • Fujian Cancer Hospital
    • Guangdong
      • Dongguan, Guangdong, China
        • Dongguan Peaple's Hospital
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-Sen University Cancer Center
      • Zhongshan, Guangdong, China
        • Zhongshan city Peaple's Hospital
    • Guangxi
      • Nanning, Guangxi, China
        • Cancer Hospital of Guangxi Medical University
    • Guizhou
      • Guiyang, Guizhou, China
        • Cancer Hospital of Guizhou Medical University
    • Hubei
      • Wuhan, Hubei, China, 430071
        • Zhongnan Hospital of Wuhan University
      • Wuhan, Hubei, China, 430000
        • Renmin Hospital of Wuhan University
      • Wuhan, Hubei, China
        • Hubei Province Cancer Hosiptal
      • Wuhan, Hubei, China
        • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
      • Wuhan, Hubei, China
        • Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
    • Hunan
      • Changsha, Hunan, China, 410000
        • Hunan Cancer Hospital
      • Changsha, Hunan, China
        • Xiangya Hospital Central South University
    • Shandong
      • Jinan, Shandong, China
        • Shandong Province Cancer Hospital
    • Shanghai
      • Shanghai, Shanghai, China
        • Changhai Hospital of Shanghai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
Other Names:
  • GEM
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
Other Names:
  • DDP
Radiation: Intensity-modulated radiotherapy
Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Other Names:
  • IMRT
Experimental: 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.
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.
Other Names:
  • PD-1/CTLA-4 bi-specific antibody
Drug: Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
Other Names:
  • GEM
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
Other Names:
  • DDP
Radiation: Intensity-modulated radiotherapy
Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Other Names:
  • IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure-free survival (FFS) in intention-to-treat population
Time Frame: 3 years
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
Time Frame: 3 years
multiple endpoint 2: calculated from randomization to the date of death from any cause.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 3 years
Graded according to CTCAE V5.0.
3 years
Distant metastasis-free survival (DMFS)
Time Frame: 3 years
calculated from randomization to the date of first distant metastasis.
3 years
Locoregional recurrence-free survival (LRRFS)
Time Frame: 3 years
calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.
3 years
Failure-free survival (FFS) within different subgroups
Time Frame: 3 years
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
Failure-free survival (FFS) in per-protocol population
Time Frame: 3 years
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 per-protocol population
Time Frame: 3 years
calculated from randomization to the date of death from any cause.
3 years
Quality of life (QoL)
Time Frame: week 1, 20, 40, 64
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.
week 1, 20, 40, 64
Tumor response
Time Frame: Through study completion, an average of 1.2 year
Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians
Through study completion, an average of 1.2 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between pre-treatment PD-L1 expression level and FFS
Time Frame: 3 years
Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing.
3 years
Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level
Time Frame: 3 years
Subgroup analysis
3 years
Evaluate failure-free survival in the subgroup of clinical stage
Time Frame: 3 years
Subgroup analysis
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Akeso Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Jun Ma, M.D., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

October 18, 2022

First Submitted That Met QC Criteria

October 19, 2022

First Posted (Actual)

October 20, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 20, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AK104-IIT-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Complete de-identified patient data set will be submitted onto an online platform.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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