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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Penpulimab; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 296
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia
      • Chris O'Brien Lifehouse
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Public Hospital Sydney
    • St Leonards, New South Wales, Australia, 2065
      • Genesis Care North Shore
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Sir Charles Gardner
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Austin Health
• Brazil
  • Reg1
    • Barretos, Reg1, Brazil, 14784-400
      • Hospital de Cancer de Barretos - Fundacao Pio XII
    • Botafogo, Reg1, Brazil, 22250-905
      • Grupo Oncoclínicas
    • Lajeado, Reg1, Brazil, 95900-000
      • Hospital Bruno Born
    • Porto Alegre, Reg1, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Santo André, Reg1, Brazil, 09060-650
      • Centro de Estudos e Pesquisa de Hematologia
    • São Paulo, Reg1, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo (ICESP)
    • São Paulo, Reg1, Brazil, 01509-900
      • Centro de Câncer A. C. Camargo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Alberta Health Services (Tom Baker Cancer Centre)
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Hospital
• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Dongguan, Guangdong, China, 523058
      • Dongguan People's Hospital
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Guangzhou, Guangdong, China, 510655
      • The sixth affiliated hospital of Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 511400
      • Guangzhou Panyu Central Hospital
    • Guangzhou, Guangdong, China, 510260
      • Zhujiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510095
      • Affiliated Cancer Hospital and Institute of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510699
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
    • Jiangmen, Guangdong, China, 529000
      • Jiangmen Central Hospital
    • Shantou, Guangdong, China, 515041
      • Cancer Hospital of Shantou University Medical College
    • Shenzhen, Guangdong, China, 518020
      • ShenZhen People's Hospital
    • Zhanjiang, Guangdong, China, 524000
      • Affiliated Hospital of Guangdong Medical University
    • Zhuhai, Guangdong, China, 519000
      • The Fifth Affiliated Hospital of Sun Yat-sen University
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical University
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Cancer Hospital
    • Nanning, Guangxi, China, 530016
      • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Cancer Hospital
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
    • Haikou, Hainan, China, 570102
      • The First Affiliated Hospital of Hainan Medical University
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410031
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410012
      • The Second Xiangya Hospital of Central South University
    • Hengyang, Hunan, China, 421001
      • The First Affiliated Hospital of University of South China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Cancer Hospital
    • Nanchang, Jiangxi, China, 330002
      • The Second Affiliated Hospital of Nanchang University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
    • Luzhou, Sichuan, China, 646000
      • The Affiliated Hospital of Southwest Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital
    • Taizhou, Zhejiang, China, 317099
      • Taizhou Hospital of Zhejiang Province
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Georgia
    • Atlanta, Georgia, United States, 30388
      • Winship Cancer Institute/Emory University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• 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.

Exclusion Criteria:

• 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).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A (study group): Penpulimab plus cisplatin/carboplatin and gemcitabine	Drug: Penpulimab; 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.; Other Names: gemcitabine; cisplatin/carboplatin
Placebo Comparator: Group B; Group B (control group): Placebo plus cisplatin/carboplatin and gemcitabine	Drug: placebo; 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.; Other Names: gemcitabine; cisplatin/carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS assessed by BIRC based on RECIST v1.1 .	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival(OS)	OS is defined as the time from the date of randomization to death from any cause.	Up to 4 years
Objective response rate (ORR)	ORR is the proportion of subjects with CR or PR based on RECIST v1.1.	Up to 2 years
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.	Up to 2 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1;	Up to 2 years
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	From the time of informed consent signed through 90 days after the last dose of penpulimab
Maximum observed concentration (Cmax)	Serum concentrations of penpulimab in individual subjects at different time points after penpulimab administration.	From first dose of penpulimab through 30 days after last dose of penpulimab
Anti-drug antibodies (ADA)	Number and percentage of subjects with detectable anti-drug antibody (ADA).	From first dose of penpulimab through 30 days after last dose of penpulimab
PD-L1 expression	Detect PD-L1 expression in tumor samples and evaluate the correlation between PD-L1 and efficacy.	Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration).
Blood EBV level	Detect the blood EBV level at baseline and changes after administration and evaluate the correlation between EBV and efficacy	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Xiaozhong Chen, MD, Cancer Hospital of The University of Chinese Academy of Sciences; Principal Investigator: Chaosu Hu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Estimated): February 23, 2026
• Study Completion (Estimated): December 23, 2026

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine; Carboplatin; Cisplatin
• Other Study ID Numbers: AK105-304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: The study protocol and SAP will be available when the main results of this study are officially published in a scientific journal.
• IPD Sharing Access Criteria: The study protocol and SAP can be obtained by emailing to the corresponding author of the published paper.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No