A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer
- Conditions
- Locally Advanced or Metastatic NSCLC
- Interventions
- Registration Number
- NCT05990127
- Lead Sponsor
- Akeso
- 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%.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 642
- The subjects voluntarily participated in the study with full informed consent and signed written informed consent form.
- Aged ≥18 years when the subject signed the informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 3 months.
- 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).
- No prior systemic therapy for advanced or metastatic NSCLC was received.
- PD-L1 TPS < 1%.
- No EGFR sensitive mutations or ALK gene translocation alterations.
- Histologically confirmed small cell lung cancer (SCLC).
- NSCLC with driver gene mutations for approved targeted drug indications.
- Active central nervous system (CNS) metastases were present.
- Pulmonary radiation therapy > 30 Gy within 6 months prior to first dose.
- Active malignant tumors within the past 5 years, except for tumors in this study and scured local tumors.
- Pregnant or lactating women.
- Clinically significant cardiovascular or cerebrovascular disease.
- 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.
- 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.
- Known active pulmonary tuberculosis.
- Patients with active hepatitis B or active hepatitis C.
- Known medical history of immunodeficiency or positive HIV test.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tislelizumab arm Paclitaxel - AK104 arm AK104 - AK104 arm carboplatin - AK104 arm Pemetrexed - AK104 arm Paclitaxel - Tislelizumab arm Tislelizumab - Tislelizumab arm carboplatin - Tislelizumab arm Pemetrexed -
- Primary Outcome Measures
Name Time Method Overall Survival(OS) Through Database Cutoff Date (Up to approximately 39 months) OS is defined as the time from randomization to death due to any cause.
Progression-Free Survival(PFS) by investigator(INV) Through Database Cutoff Date (Up to approximately 39 months) PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1
- Secondary Outcome Measures
Name Time Method Progression-Free Survival(PFS) by Blind independent center review(BIRC) Through Database Cutoff Date (Up to approximately 39 months) PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1
Objective response rate (ORR) was assessed by INV Through Database Cutoff Date (Up to approximately 39 months) ORR is the proportion of subjects with CR or PR based on RECIST v1.1
Disease control rate (DCR) was assessed by INV Through Database Cutoff Date (Up to approximately 39 months) Disease control rate (DCR) was assessed based on RECIST V1.1 criteria
Time to response (TTR) was assessed by INV Through Database Cutoff Date (Up to approximately 39 months) The time from the first administration to the date of documented CR or PR
Duration of response (DOR) was assessed by INV Through Database Cutoff Date (Up to approximately 39 months) Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria
Objective response rate (ORR) was assessed by BIRC Through Database Cutoff Date (Up to approximately 39 months) ORR is the proportion of subjects with CR or PR based on RECIST v1.1
Disease control rate (DCR) was assessed BIRC Through Database Cutoff Date (Up to approximately 39 months) Disease control rate (DCR) was assessed based on RECIST V1.1 criteria
Time to response (TTR) was assessed by BIRC Through Database Cutoff Date (Up to approximately 39 months) The time from the first administration to the date of documented CR or PR
Duration of response (DOR) was assessed by BIRC Through Database Cutoff Date (Up to approximately 39 months) Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria
The number of subjects experiencing adverse events (AEs) Through Database Cutoff Date (Up to approximately 39 months) Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Pharmacokinetic Through Database Cutoff Date (Up to approximately 39 months) The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration
Antidrug antibodies (ADA) of AK104 Through Database Cutoff Date (Up to approximately 39 months) Proportion of subjects who develop detectable anti-drug antibodies (ADAs)
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) Through Database Cutoff Date (Up to approximately 39 months) EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
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) Through Database Cutoff Date (Up to approximately 39 months) EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". For symptoms scales, higher scores indicated greater symptom burden.
Trial Locations
- Locations (62)
The Second Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Cancer hospital, Chinese academy of medical sciences and Peking union medical college
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Anhui provincial cancer hospital
🇨🇳Hefei, Anhui, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Hainan cancer hospital
🇨🇳Haikou, Hainan, China
The Fourth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Tangshang people's hospital
🇨🇳Tangshan, Hebei, China
Harbin medical university cancer hospital
🇨🇳Harbin, Heilongjiang, China
Jiamusi Tuberculosis Prevention and Control Hospital (Jiamusi Cancer Hospital)
🇨🇳Jiamusi, Heilongjiang, China
The First Affiliated Hospital of Xinxiang Medical College
🇨🇳Xinxiang, Henan, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The affiliated hospital of xuzhou medical university
🇨🇳Xuzhou, Jiangsu, China
First Affiliated Hospital of Gannan medical college
🇨🇳Ganzhou, Jiangxi, China
First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Binzhou medical university hospital
🇨🇳Binzhou, Shandong, China
Tonghua Central Hospital
🇨🇳Tonghua, Jilin, China
General hospital of ningxia medical university
🇨🇳Yinchuan, Ningxia, China
Zhongshan Hospital, Fudan university
🇨🇳Shanghai, Shanghai, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
Weifang NO.2 people's Hospital
🇨🇳Weifang, Shandong, China
Changzhi people's hospital
🇨🇳Changzhi, Shanxi, China
Shanxi Cancer hospital
🇨🇳Taiyuan, Shanxi, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
The Second People's Hospital of Yibin City
🇨🇳Yibin, Sichuan, China
Tianjin Chest Hospital
🇨🇳Tianjin, Tianjin, China
Xinjiang Medical University Cancer Hospital
🇨🇳Urumqi, Xinjiang, China
Yunnan Cancer Hospital /the Third Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The first affiliated hospital of bengbu medical college
🇨🇳Bengbu, Anhui, China
Anhui provincial hospital
🇨🇳Hefei, Anhui, China
The first affiliated hospital of wannan medical college
🇨🇳Wuhu, Anhui, China
The Fifth Medical Center of the Chinese People's Liberation Army General Hospital
🇨🇳Beijing, Beijing, China
Zhangzhou municipal hospital of fujian province
🇨🇳Zhangzhou, Fujian, China
Gansu provincial cancer hospital
🇨🇳Lanzhou, Gansu, China
Cancer hospital Chinses academy of medical sciences， shenzhen center
🇨🇳Shenzhen, Guangdong, China
Nanfang hospital
🇨🇳Guangzhou, Guangdong, China
Affiliated hospital of Hebei university
🇨🇳Baoding, Hebei, China
The second people's hospital of Hengshui
🇨🇳Hengshui, Hebei, China
The Second Hospital of HeBei Medical University
🇨🇳Shijiazhuang, Hebei, China
The first hospital of Qiqihar
🇨🇳Qiqihar, Heilongjiang, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
Nanyang central hospital
🇨🇳Nanyang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
The first hospital of Jilin Universit
🇨🇳Changchun, Jilin, China
Qinghai university affiliated hospital
🇨🇳Xining, Qinghai, China
Sichuan Cancer Hospital
🇨🇳Chengdu, Sichuan, China
Mianyang central hospital
🇨🇳Mianyang, Sichuan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
The First Hospital of China medical University
🇨🇳Shenyang, Liaoning, China
Liaoning cancer hospital
🇨🇳Shenyang, Liaoning, China
Beijing Chest hospital
🇨🇳Beijing, Beijing, 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
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Fujian cancer hospital
🇨🇳Fuzhou, Fujian, China