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Nasopharyngeal CarcinomaPhase 3GEMSTONENCT05587374

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

A Phase 3 study testing Cadonilimab, Gemcitabine and Cisplatin in people with Nasopharyngeal Carcinoma and Nasopharyngeal Cancer, run by Sun Yat-sen University at 18 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Cadonilimab, Gemcitabine and Cisplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
490 participants
Where
18 sitesChina
Study dates
1 Aug 2023to 1 Aug 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

China18 sites

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality

  • The First Affiliated Hospital of Bengbu Medical College

    Bengbu, Anhui, 233000

  • Hunan Cancer Hospital

    Changsha, Hunan, 410000

  • Xiangya Hospital Central South University

    Changsha, Hunan

  • Dongguan Peaple's Hospital

    Dongguan, Guangdong

  • Fujian Cancer Hospital

    Fuzhou, Fujian

  • Sun Yat-Sen University Cancer Center

    Guangzhou, Guangdong, 510060

  • Cancer Hospital of Guizhou Medical University

    Guiyang, Guizhou

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

    Hefei, Anhui, 230041

  • Shandong Province Cancer Hospital

    Jinan, Shandong

  • Cancer Hospital of Guangxi Medical University

    Nanning, Guangxi

  • Changhai Hospital of Shanghai

    Shanghai, Shanghai Municipality

  • Renmin Hospital of Wuhan University

    Wuhan, Hubei, 430000

  • Zhongnan Hospital of Wuhan University

    Wuhan, Hubei, 430071

  • Hubei Province Cancer Hosiptal

    Wuhan, Hubei

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

    Wuhan, Hubei

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

    Wuhan, Hubei

  • Zhongshan city Peaple's Hospital

    Zhongshan, Guangdong

Other trials in China

About this study

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

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).

Read the 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).

Being tested
Cadonilimab, Gemcitabine, Cisplatin, Intensity-modulated radiotherapy
Keywords
immunotherapy, PD-1/CTLA-4 Bi-specific Antibody, Chemoradiotherapy
Medical subject headings
Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CadonilimabDrug

    Also called PD-1/CTLA-4 bi-specific antibody

    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.

  • GemcitabineDrug

    Also called GEM

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

  • CisplatinDrug

    Also called DDP

    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 radiotherapyRadiation

    Also called IMRT

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

Study groups in NCT05587374
Study groupRoleWhat they receive
Cadonilimab armExperimentalPatients 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.
Receives: Drug: Cadonilimab; Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy
Chemoradiation armActive comparatorPatients 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.
Receives: Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 3 years

  2. Overall survival (OS) in intention-to-treat population

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

    Measured: 3 years

Secondary outcomes (8)

  1. Failure-free survival (FFS) in per-protocol population

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

    Measured: 3 years

  2. Overall survival (OS) in per-protocol population

    calculated from randomization to the date of death from any cause.

    Measured: 3 years

  3. Locoregional recurrence-free survival (LRRFS)

    calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.

    Measured: 3 years

  4. Distant metastasis-free survival (DMFS)

    calculated from randomization to the date of first distant metastasis.

    Measured: 3 years

  5. Adverse events (AEs) and serious adverse events (SAEs)

    Graded according to CTCAE V5.0.

    Measured: 3 years

  6. 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.

    Measured: week 1, 20, 40, 64

  7. 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).

    Measured: 3 years

  8. Tumor response

    Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians

    Measured: Through study completion, an average of 1.2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2022
  2. Study start1 Aug 2023
  3. Primary completion1 Aug 2027 (estimated)
  4. Study completion1 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
490 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05587374
Sponsor's protocol ID
AK104-IIT-019
Acronym
GEMSTONE
Status last verified
Jan 2025
First submitted
18 Oct 2022
Last updated
23 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Complete de-identified patient data set will be submitted onto an online platform.

Publications

  • 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.

    PubMed 31150573

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

    PubMed 35986837

  • 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.

    PubMed 28837405

  • 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.

    PubMed 29584545

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cadonilimab, Gemcitabine and Cisplatin in people with Nasopharyngeal Carcinoma and Nasopharyngeal Cancer, run by Sun Yat-sen University at 18 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Failure-free survival (FFS) in intention-to-treat population (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05587374, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.

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