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

Nasopharyngeal Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04974398
• Other study ID #: AK105-304
• Status: Recruiting
• Phase: Phase 3
• Start date: August 16, 2021
• Est. completion date: September 15, 2026

Study information

• Verified date: April 2024
• Source: Akeso
• Contact: Zhifang Yao, MD
• Phone: +86-0760-89873999
• Email: clinicaltrials[@]akesobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 298
• Est. completion date: September 15, 2026
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

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; or nasopharyngeal carcinoma subjects who have a local-regional recurrence and/or distant metastasis more than 6 months after the end of previous radical treatment (radiotherapy with induction, concurrent, adjuvant chemotherapy);No systemic treatment has been received for recurrent or metastatic nasopharyngeal carcinoma, and local regional recurrence is not suitable for local treatment or has received local treatment.
• 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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

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

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	St Vincent's Public Hospital Sydney	Darlinghurst	New South Wales
Australia	Sir Charles Gardner	Heidelberg	Victoria
Australia	Austin Health	Nedlands	Western Australia
Australia	Genesis Care North Shore	St Leonards	New South Wales
Brazil	Hospital de Câncer de Barretos - Fundação Pio XII	Barretos	Reg1
Brazil	Grupo Oncoclínicas	Botafogo	Reg1
Brazil	Hospital Bruno Born	Lajeado	Reg1
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	Reg1
Brazil	Centro de Estudos e Pesquisa de Hematologia	Santo André	Reg1
Brazil	Centro de Câncer A. C. Camargo	São Paulo	Reg1
Brazil	Instituto do Câncer do Estado de São Paulo (ICESP)	São Paulo	Reg1
Canada	Alberta Health Services (Tom Baker Cancer Centre)	Calgary	Alberta
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Sichuan Cancer Hospital	Chengdu	Sichuan
China	Dongguan People's Hospital	Dongguan	Guangdong
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Affiliated Cancer Hospital and Institute of Guangzhou Medical University	Guangzhou	Guangdong
China	Guangzhou Panyu Central Hospital	Guangzhou	Guangdong
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Affiliated Hospital of Guilin Medical University	Guilin	Guangxi
China	Guizhou Cancer Hospital	Guiyang	Guizhou
China	Hainan General Hospital	Haikou	Hainan
China	The First Affiliated Hospital of Hainan Medical University	Haikou	Hainan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affiliated Hospital of University of South China	Hengyang	Hunan
China	Jiangmen Central Hospital	Jiangmen	Guangdong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Guangxi Medical University Cancer Hospital	Nanning	Guangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	The Fifth Affiliated Hospital of Sun Yat-sen University	Zhuhai	Guangdong
United States	University of Michigan	Ann Arbor	Michigan
United States	Winship Cancer Institute/Emory University	Atlanta	Georgia
United States	City of Hope	Duarte	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS assessed by BIRC based on RECIST v1.1 .	Up to 2 years
Secondary	Overall survival(OS)	OS is defined as the time from the date of randomization to death from any cause.	Up to 4 years
Secondary	Objective response rate (ORR)	ORR is the proportion of subjects with CR or PR based on RECIST v1.1.	Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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).
Secondary	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