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Nasopharyngeal CarcinomaPhase 3NCT04974398

A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma

A Phase 3 study testing Penpulimab in people with Nasopharyngeal Carcinoma, run by Akeso at 56 sites in 5 countries.

Active, not recruiting

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

Official record
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Trial summary

This study is a randomized, double-blind, multi-center phase III clinical study to compare the efficacy and safety of penpulimab combined with chemotherapy and placebo combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. Read more about this study

Who is it for?
Ages 12 to 75 years
Conditions the study is for
Nasopharyngeal Carcinoma
What is being tested?
Penpulimab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
296 participants
Where
56 sitesin 5 countries
Study dates
16 Aug 2021to 23 Dec 2026
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 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Voluntarily signed written Informed Consent Form(ICF).
  • Main study: Age of ≥ 18 years and ≤ 75 years at the time of enrollment.
  • Substudy: Age of ≥ 12 years and < 18 years. Weight≥ 35KG.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Expected survival of ≥ 3 months.
  • Histologically or cytologically confirmed nasopharyngeal carcinoma.
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  • Subjects with primary metastatic (nasopharyngeal carcinoma, stage IVB defined by the Union for International Cancer Control and the American Joint Committee on Cancer Staging System edition 8) nasopharyngeal carcinoma who are not suitable for local treatment or radical treatment; subjects who have a local-regional recurrence and/or distant metastasis more than 6 months after the completion of prior radical treatment (radiotherapy with induction, concurrent, adjuvant chemotherapy)； No systemic treatment has been received for recurrent or metastatic diseases, not amendable to local treatment or have received local treatment for the local-regional recurrent disease
  • At least one measurable lesion according to RECIST v1.1;
  • Has adequate organ function.
  • All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 150 days after the last dose of study treatment.

Who cannot join

  • Subjects with pathologically diagnosed nasopharyngeal adenocarcinoma or sarcoma.
  • Subjects have had another malignancy within 3 years before the first dose, except nasopharyngeal carcinoma. Subjects with other malignancies that have been cured by local therapy such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervix or breast carcinoma in situ are not excluded.
  • Participation in treatment with an investigational drug or use of an investigational device within 4 weeks before first study dosing.
  • Have previously received immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists , immune cell therapy, and other treatments against tumor immune mechanism.
  • Active autoimmune disease requiring systemic treatment within 2 years prior to initial administration, or as an autoimmune disease that can recur or for which treatment is planned determined by the investigator.
  • Active or past history of definite inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
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  • History of immunodeficiency; those who test positive for HIV antibody; current chronic use of systemic corticosteroids or immunosuppressive agents.
  • Known active tuberculosis (TB) (suspected of having active TB need to undergo clinical examination for exclusion of such possibility); known active syphilis infection.
  • Known history of allotransplantation and allogeneic hematopoietic stem cell transplantation.
  • Has known active Hepatitis B or Hepatitis C.
  • Active or untreated CNS metastases.
  • Subjects with peripheral neuropathy.
  • Unresolved toxicity from prior anti-tumor therapy, defined as toxicity that has not recovered .
  • Received a live vaccine within 30 days before the first dose or planned to receive a live vaccine during the study.
  • Known allergy to any study drug component; known history of serious hypersensitivity to other monoclonal antibodies.
  • Pregnant or nursing (lactating) women.

Trial locations and contacts

56 sites in 5 countries.

56 sites in 5 countries

China37 sites

  • The Second Xiangya Hospital of Central South University

    Changsha, Hunan, 410012

  • Hunan Cancer Hospital

    Changsha, Hunan, 410031

  • Sichuan Cancer Hospital

    Chengdu, Sichuan, 610042

  • Dongguan People's Hospital

    Dongguan, Guangdong, 523058

  • Fujian Cancer Hospital

    Fuzhou, Fujian, 350014

  • The First Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510080

  • Affiliated Cancer Hospital and Institute of Guangzhou Medical University

    Guangzhou, Guangdong, 510095

  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510120

  • The First Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong, 510120

  • Zhujiang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510260

  • Nanfang Hospital, Southern Medical University

    Guangzhou, Guangdong, 510515

  • The Sixth Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510655

  • The First Affiliated Hospital of Guangdong Pharmaceutical University

    Guangzhou, Guangdong, 510699

  • Guangzhou Panyu Central Hospital

    Guangzhou, Guangdong, 511400

  • Affiliated Hospital of Guilin Medical University

    Guilin, Guangxi, 541001

  • Guizhou Cancer Hospital

    Guiyang, Guizhou, 550000

  • The First Affiliated Hospital of Hainan Medical University

    Haikou, Hainan, 570102

  • Hainan General Hospital

    Haikou, Hainan, 570311

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310005

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui, 230022

  • The First Affiliated Hospital of University of South China

    Hengyang, Hunan, 421001

  • Jiangmen Central Hospital

    Jiangmen, Guangdong, 529000

  • Yunnan Cancer Hospital

    Kunming, Yunnan, 650118

  • The Affiliated Hospital of Southwest Medical University

    Luzhou, Sichuan, 646000

  • The Second Affiliated Hospital of Nanchang University

    Nanchang, Jiangxi, 330002

  • Jiangxi Cancer Hospital

    Nanchang, Jiangxi, 330029

  • The People's Hospital of Guangxi Zhuang Autonomous Region

    Nanning, Guangxi, 530016

  • Guangxi Medical University Cancer Hospital

    Nanning, Guangxi, 530021

  • The First Affiliated Hospital of Guangxi Medical University

    Nanning, Guangxi, 530021

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200032

  • Cancer Hospital of Shantou University Medical College

    Shantou, Guangdong, 515041

  • Shenzhen People's Hospital

    Shenzhen, Guangdong, 518020

  • Taizhou Hospital of Zhejiang Province

    Taizhou, Zhejiang, 317099

  • Hubei Cancer Hospital

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

  • Affiliated Hospital of Guangdong Medical University

    Zhanjiang, Guangdong, 524000

  • The Fifth Affiliated Hospital of Sun Yat-sen University

    Zhuhai, Guangdong, 519000

Other trials in China

Brazil7 sites

  • Hospital de Câncer de Barretos - Fundação Pio XII

    Barretos, REG1, 14784-400

  • Grupo Oncoclínicas

    Botafogo, REG1, 22250-905

  • Hospital Bruno Born

    Lajeado, REG1, 95900-000

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, REG1, 91350-200

  • Centro de Estudos e Pesquisa de Hematologia

    Santo André, REG1, 09060-650

  • Instituto do Câncer do Estado de São Paulo (ICESP)

    São Paulo, REG1, 01246-000

  • Centro de Câncer A. C. Camargo

    São Paulo, REG1, 01509-900

Other trials in Brazil

United States5 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Winship Cancer Institute/Emory University

    Atlanta, Georgia, 30388

  • City of Hope

    Duarte, California, 91010

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

Australia5 sites

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales

  • St Vincent's Public Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Sir Charles Gardner

    Heidelberg, Victoria, 3084

  • Austin Health

    Nedlands, Western Australia, 6009

  • Genesis Care North Shore

    St Leonards, New South Wales, 2065

Other trials in Australia

Canada2 sites

  • Alberta Health Services (Tom Baker Cancer Centre)

    Calgary, Alberta, T2N 4N2

  • Toronto Sunnybrook Hospital

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: A Randomized, Double-blind, Multi-center Phase III Study of Penpulimab (AK105) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma

This study is a randomized, double-blind, multi-center phase III clinical study to compare the efficacy and safety of penpulimab combined with chemotherapy and placebo combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma.

Being tested
Penpulimab, placebo
Medical subject headings
Nasopharyngeal Carcinoma

What participants receive

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

  • PenpulimabDrug

    Also called cisplatin/carboplatin, gemcitabine

    Arm A: Penpulimab (200 mg, administered on Day 1 of each cycle, Q3W) +cisplatin (80 mg/m2) or carboplatin (AUC 5) (administered on Day 1 of each cycle, Q3W, up to 6 cycles) + gemcitabine (1000 mg/ m2, administered on Days 1 and 8 of each cycle, Q3W, up to 6 cycles), 3 weeks (21 days) per cycle; followed by penpulimab (200 mg, administered on Day 1 of each cycle, Q3W) as maintenance treatment.

  • placeboDrug

    Also called cisplatin/carboplatin, gemcitabine

    Arm B: Placebo (200 mg, administered on Day 1 of each cycle, Q3W) + cisplatin (80 mg/m2) or carboplatin (AUC 5) (administered on Day 1 of each cycle, Q3W, up to 6 cycles) + gemcitabine (1000 mg/m2, administered on Days 1 and 8 of each cycle, Q3W, up to 6 cycles), every 3 weeks (21 days) per cycle; followed by placebo(200 mg, administered on Day 1 of each cycle, Q3W) as maintenance treatment. Subjects in Arm B will have the opportunity to crossover to openlabel treatment with penpulimab monotherapy after radiographic disease progression.

Study groups in NCT04974398
Study groupRoleWhat they receive
Group AExperimentalGroup A (study group): Penpulimab plus cisplatin/carboplatin and gemcitabine
Receives: Drug: Penpulimab
Group BPlacebo comparatorGroup B (control group): Placebo plus cisplatin/carboplatin and gemcitabine
Receives: Drug: placebo

What is being measured

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

  1. Progression-free survival (PFS)

    PFS assessed by BIRC based on RECIST v1.1 .

    Measured: Up to 2 years

Secondary outcomes (9)

  1. Overall survival(OS)

    OS is defined as the time from the date of randomization to death from any cause.

    Measured: Up to 4 years

  2. Objective response rate (ORR)

    ORR is the proportion of subjects with CR or PR based on RECIST v1.1.

    Measured: Up to 2 years

  3. Duration of response (DoR)

    DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

    Measured: Up to 2 years

  4. Disease control rate (DCR)

    DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1;

    Measured: Up to 2 years

  5. Adverse event (AE)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment

    Measured: From the time of informed consent signed through 90 days after the last dose of penpulimab

  6. Maximum observed concentration (Cmax)

    Serum concentrations of penpulimab in individual subjects at different time points after penpulimab administration.

    Measured: From first dose of penpulimab through 30 days after last dose of penpulimab

  7. Anti-drug antibodies (ADA)

    Number and percentage of subjects with detectable anti-drug antibody (ADA).

    Measured: From first dose of penpulimab through 30 days after last dose of penpulimab

  8. PD-L1 expression

    Detect PD-L1 expression in tumor samples and evaluate the correlation between PD-L1 and efficacy.

    Measured: Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration).

  9. Blood EBV level

    Detect the blood EBV level at baseline and changes after administration and evaluate the correlation between EBV and efficacy

    Measured: Up to 2 years

Timeline

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

  1. First posted23 Jul 2021
  2. Study start16 Aug 2021
  3. Primary completion23 Feb 2026 (estimated)
  4. Study completion23 Dec 2026 (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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
296 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04974398
Sponsor's protocol ID
AK105-304
Status last verified
Apr 2025
First submitted
13 Jul 2021
Last updated
13 Apr 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual anonymized participant data will be considered for sharing once the product and indication have been approved by major health authorities, if there is legal authority to share the data and there is no reasonable likelihood of participant reidentification. Data may be requested from the corresponding author.

Publications

  • Huang S, Liu F, Qu S, Chen L, Zhou P, Qu S, Ai X, Chen Y, Liu M, Wang R, Chan KK, Zhang P, Hu C, Wen J, Zhang J, Lin Q, Li X, Gu K, Xiang L, Wang D, Li J, Lin D, Hu D, Ding J, Wang S, Huang X, Wang L, Jin F, Pfister DG, Mak MP, Marchi PRM, Jiang Y, Yang H, Hu X, Liu T, Wu D, Shreenivas A, Oliveira TB, Silva CEB, Alves GV, Li X, Yao Z, Lu D, Hu M, Wang ZM, Li B, Xia M, Chen X, Hu C, Xu T. Anti-PD-1 antibody penpulimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: a randomized, double-blind phase 3 study. Signal Transduct Target Ther. 2026 Apr 8;11(1):126. doi: 10.1038/s41392-026-02645-0.

    PubMed 41946687

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Penpulimab in people with Nasopharyngeal Carcinoma, run by Akeso at 56 sites in 5 countries.

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 10 inclusion and 16 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 13 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in China, Brazil, United States, Australia, Canada. 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. Some participants in this study may receive a placebo. 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?

Progression-free survival (PFS) (time frame: Up to 2 years). 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 NCT04974398, which also lists 1 linked publication.

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 13 Apr 2025.

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