A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
- Conditions
- Nasopharyngeal Carcinoma
- Interventions
- Drug: placebo
- Registration Number
- NCT04974398
- Lead Sponsor
- Akeso
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 296
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A Penpulimab Group A (study group): Penpulimab plus cisplatin/carboplatin and gemcitabine Group B placebo Group B (control group): Placebo plus cisplatin/carboplatin and gemcitabine
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to 2 years PFS assessed by BIRC based on RECIST v1.1 .
- Secondary Outcome Measures
Name Time Method Duration of response (DoR) Up to 2 years 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.
PD-L1 expression Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration). Detect PD-L1 expression in tumor samples and evaluate the correlation between PD-L1 and efficacy.
Disease control rate (DCR) Up to 2 years DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1;
Maximum observed concentration (Cmax) From first dose of penpulimab through 30 days after last dose of penpulimab Serum concentrations of penpulimab in individual subjects at different time points after penpulimab administration.
Blood EBV level Up to 2 years Detect the blood EBV level at baseline and changes after administration and evaluate the correlation between EBV and efficacy
Overall survival(OS) Up to 4 years OS is defined as the time from the date of randomization to death from any cause.
Objective response rate (ORR) Up to 2 years ORR is the proportion of subjects with CR or PR based on RECIST v1.1.
Adverse event (AE) From the time of informed consent signed through 90 days after the last dose of penpulimab 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
Anti-drug antibodies (ADA) From first dose of penpulimab through 30 days after last dose of penpulimab Number and percentage of subjects with detectable anti-drug antibody (ADA).
Trial Locations
- Locations (56)
Grupo Oncoclínicas
🇧🇷Botafogo, Reg1, Brazil
Hospital Bruno Born
🇧🇷Lajeado, Reg1, Brazil
City of Hope
🇺🇸Duarte, California, United States
Winship Cancer Institute/Emory University
🇺🇸Atlanta, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
St Vincent's Public Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Genesis Care North Shore
🇦🇺St Leonards, New South Wales, Australia
Sir Charles Gardner
🇦🇺Heidelberg, Victoria, Australia
Austin Health
🇦🇺Nedlands, Western Australia, Australia
Hospital de Câncer de Barretos - Fundação Pio XII
🇧🇷Barretos, Reg1, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, Reg1, Brazil
Centro de Estudos e Pesquisa de Hematologia
🇧🇷Santo André, Reg1, Brazil
Instituto do Câncer do Estado de São Paulo (ICESP)
🇧🇷São Paulo, Reg1, Brazil
Centro de Câncer A. C. Camargo
🇧🇷São Paulo, Reg1, Brazil
Alberta Health Services (Tom Baker Cancer Centre)
🇨🇦Calgary, Alberta, Canada
Toronto Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Dongguan People's Hospital
🇨🇳Dongguan, Guangdong, China
The First Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Affiliated Cancer Hospital and Institute of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Sixth Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangdong Pharmaceutical University
🇨🇳Guangzhou, Guangdong, China
Guangzhou Panyu Central Hospital
🇨🇳Guangzhou, Guangdong, China
Jiangmen Central Hospital
🇨🇳Jiangmen, Guangdong, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
Shenzhen People's Hospital
🇨🇳Shenzhen, Guangdong, China
Affiliated Hospital of Guangdong Medical University
🇨🇳Zhanjiang, Guangdong, China
The Fifth Affiliated Hospital of Sun Yat-sen University
🇨🇳Zhuhai, Guangdong, China
Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi, China
The People's Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Guizhou Cancer Hospital
🇨🇳Guiyang, Guizhou, China
The First Affiliated Hospital of Hainan Medical University
🇨🇳Haikou, Hainan, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of University of South China
🇨🇳Hengyang, Hunan, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, Jiangxi, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Sichuan Cancer Hospital
🇨🇳Chengdu, Sichuan, China
The Affiliated Hospital of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Taizhou Hospital of Zhejiang Province
🇨🇳Taizhou, Zhejiang, China