Clinical trial NCT05990127: A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer
Official title: A Randomized, Double-blind, Phase III Trial to Compare the Efficacy and Safety of AK104 Combined With Chemotherapy to Tislelizumab Combined With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Locally Advanced or Metastatic NSCLC
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2023-08-14
Enrollment: 642
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, phase III clinical study to compare the efficacy and safety of AK104 combined chemotherapy versus Tislelizumab combined chemotherapy in first-line treatment of Locally advanced or metastatic NSCLC with PD-L1 TPS \< 1%.


Eligibility criteria: Inclusion Criteria:

1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form.
2. Aged ≥18 years when the subject signed the informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Life expectancy ≥ 3 months.
5. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) that not amenable to complete surgical resection and not amenable to radical concurrent/sequential chemoradiation or metastatic (Stage IV) NSCLC (American Joint Committee on Cancer \[AJCC\] 8th edition).
6. No prior systemic therapy for advanced or metastatic NSCLC was received.
7. PD-L1 TPS \< 1%.
8. No EGFR sensitive mutations or ALK gene translocation alterations.

Exclusion Criteria:

1. Histologically confirmed small cell lung cancer (SCLC).
2. NSCLC with driver gene mutations for approved targeted drug indications.
3. Active central nervous system (CNS) metastases were present.
4. Pulmonary radiation therapy \> 30 Gy within 6 months prior to first dose.
5. Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors.
6. Pregnant or lactating women.
7. Clinically significant cardiovascular or cerebrovascular disease.
8. Subjects with a known history of severe hypersensitivity to other monoclonal antibodies. A known history of allergy or hypersensitivity to all investigational drugs or any of their components.
9. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.
10. Known active pulmonary tuberculosis.
11. Patients with active hepatitis B or active hepatitis C.
12. Known medical history of immunodeficiency or positive HIV test.

Primary outcomes:
measure: Overall Survival(OS)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Progression-Free Survival(PFS) by investigator(INV)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
Secondary outcomes:
measure: Progression-Free Survival(PFS) by Blind independent center review(BIRC)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Objective response rate (ORR) was assessed by INV
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Disease control rate (DCR) was assessed by INV
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Time to response (TTR) was assessed by INV
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Duration of response (DOR) was assessed by INV
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Objective response rate (ORR) was assessed by BIRC
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Disease control rate (DCR) was assessed BIRC
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Time to response (TTR) was assessed by BIRC
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Duration of response (DOR) was assessed by BIRC
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: The number of subjects experiencing adverse events (AEs)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Pharmacokinetic
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Antidrug antibodies (ADA) of AK104
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
measure: Health-related Quality of Life (HRQoL) assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29)
timeFrame: Through Database Cutoff Date (Up to approximately 39 months)
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Hefei
country: China
facility: Anhui provincial hospital
state: Anhui
city: Hefei
country: China
facility: Anhui provincial cancer hospital
state: Anhui
city: Wuhu
country: China
facility: The first affiliated hospital of wannan medical college
state: Anhui
city: Beijing
country: China
facility: Cancer hospital, Chinese academy of medical sciences and Peking union medical college
state: Beijing
city: Beijing
country: China
facility: The Fifth Medical Center of the Chinese People's Liberation Army General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian cancer hospital
state: Fujian
city: Zhangzhou
country: China
facility: Zhangzhou municipal hospital of fujian province
state: Fujian
city: Lanzhou
country: China
facility: Gansu provincial cancer hospital
state: Gansu
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: Nanfang hospital
state: Guangdong
city: Shenzhen
country: China
facility: Cancer hospital Chinses academy of medical sciences， shenzhen center
state: Guangdong
city: Haikou
country: China
facility: Hainan cancer hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated hospital of Hebei university
state: Hebei
city: Hengshui
country: China
facility: The second people's hospital of Hengshui
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of HeBei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshang people's hospital
state: Hebei
city: Harbin
country: China
facility: Harbin medical university cancer hospital
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Tuberculosis Prevention and Control Hospital (Jiamusi Cancer Hospital)
state: Heilongjiang
city: Qiqihar
country: China
facility: The first hospital of Qiqihar
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang central hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital, Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: The affiliated hospital of xuzhou medical university
state: Jiangsu
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan medical college
state: Jiangxi
city: Nanchang
country: China
facility: First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The first hospital of Jilin Universit
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning cancer hospital
state: Liaoning
city: Yinchuan
country: China
facility: General hospital of ningxia medical university
state: Ningxia
city: Xining
country: China
facility: Qinghai university affiliated hospital
state: Qinghai
city: Binzhou
country: China
facility: Binzhou medical university hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weifang
country: China
facility: Weifang NO.2 people's Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan university
state: Shanghai
city: Changzhi
country: China
facility: Changzhi people's hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cancer hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Mianyang
country: China
facility: Mianyang central hospital
state: Sichuan
city: Yibin
country: China
facility: The Second People's Hospital of Yibin City
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Chest Hospital
state: Tianjin
city: Urumqi
country: China
facility: Xinjiang Medical University Cancer Hospital
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital /the Third Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Cancer hospital, Chinese academy of medical sciences and Peking union medical college
name: Jie Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Cancer Hospital
name: Qingming Wang
role: PRINCIPAL_INVESTIGATOR
References: