Clinical trial NCT04974398: A Study of Penpulimab (AK105) in the First-line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-07-23
Enrollment: 296
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall survival(OS)
timeFrame: Up to 4 years
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Adverse event (AE)
timeFrame: From the time of informed consent signed through 90 days after the last dose of penpulimab
measure: Maximum observed concentration (Cmax)
timeFrame: From first dose of penpulimab through 30 days after last dose of penpulimab
measure: Anti-drug antibodies (ADA)
timeFrame: From first dose of penpulimab through 30 days after last dose of penpulimab
measure: PD-L1 expression
timeFrame: Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration).
measure: Blood EBV level
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute/Emory University
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Public Hospital Sydney
state: New South Wales
city: St Leonards
country: Australia
facility: Genesis Care North Shore
state: New South Wales
city: Heidelberg
country: Australia
facility: Sir Charles Gardner
state: Victoria
city: Nedlands
country: Australia
facility: Austin Health
state: Western Australia
city: Barretos
country: Brazil
facility: Hospital de Câncer de Barretos - Fundação Pio XII
state: Reg1
city: Botafogo
country: Brazil
facility: Grupo Oncoclínicas
state: Reg1
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
state: Reg1
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Reg1
city: Santo André
country: Brazil
facility: Centro de Estudos e Pesquisa de Hematologia
state: Reg1
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo (ICESP)
state: Reg1
city: São Paulo
country: Brazil
facility: Centro de Câncer A. C. Camargo
state: Reg1
city: Calgary
country: Canada
facility: Alberta Health Services (Tom Baker Cancer Centre)
state: Alberta
city: Toronto
country: Canada
facility: Toronto Sunnybrook Hospital
state: Ontario
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and Institute of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Panyu Central Hospital
state: Guangdong
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Cancer Hospital
state: Guizhou
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical University
state: Hainan
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Chaosu Hu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cancer Hospital of The University of Chinese Academy of Sciences
name: Xiaozhong Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: