A Study of AK104/Tislelizumab With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer

Locally Advanced or Metastatic NSCLC Clinical Trial

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05990127
• Other study ID #: AK104-307
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 14, 2023
• Est. completion date: November 28, 2026

Study information

• Verified date: August 2023
• Source: Akeso
• Contact: Zhifang Yao, M.D.
• Phone: +86-0760-89873999
• Email: clinicaltrials[@]akesobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 642
• Est. completion date: November 28, 2026
• Est. primary completion date: August 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Locally Advanced or Metastatic NSCLC

Intervention

Drug:
• AK104
AK104 IV, q3w
• Tislelizumab
Tislelizumab IV, q3w
• carboplatin
carboplatin IV, q3w
• Pemetrexed
Pemetrexed IV, q3w (for Nonsquamous NSCLC)
• Paclitaxel
Paclitaxel IV, q3w (for squamous NSCLC)

Locations

Country	Name	City	State
China	Affiliated hospital of Hebei university	Baoding	Hebei
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chest hospital	Beijing	Beijing
China	Cancer hospital, Chinese academy of medical sciences and Peking union medical college	Beijing	Beijing
China	The Fifth Medical Center of the Chinese People's Liberation Army General Hospital	Beijing	Beijing
China	The first affiliated hospital of bengbu medical college	Bengbu	Anhui
China	Binzhou medical university hospital	Binzhou	Shandong
China	The first hospital of Jilin Universit	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital, Central South University	Changsha	Hunan
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Changzhi people's hospital	Changzhi	Shanxi
China	Sichuan Cancer Hospital	Chengdu	Sichuan
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Fujian cancer hospital	Fuzhou	Fujian
China	First Affiliated Hospital of Gannan medical college	Ganzhou	Jiangxi
China	Affiliated cancer hospital and institute of guangzhou medical university	Guangzhou	Guangdong
China	Nanfang hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Hainan cancer hospital	Haikou	Hainan
China	The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin medical university cancer hospital	Harbin	Heilongjiang
China	Anhui provincial cancer hospital	Hefei	Anhui
China	Anhui provincial hospital	Hefei	Anhui
China	The second people's hospital of Hengshui	Hengshui	Hebei
China	Jiamusi Tuberculosis Prevention and Control Hospital (Jiamusi Cancer Hospital)	Jiamusi	Heilongjiang
China	Shandong Cancer Hospital	Jinan	Shandong
China	Yunnan Cancer Hospital /the Third Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Gansu provincial cancer hospital	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Mianyang central hospital	Mianyang	Sichuan
China	First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Nanyang central hospital	Nanyang	Henan
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	The first hospital of Qiqihar	Qiqihar	Heilongjiang
China	Zhongshan Hospital, Fudan university	Shanghai	Shanghai
China	Liaoning cancer hospital	Shenyang	Liaoning
China	The First Hospital of China medical University	Shenyang	Liaoning
China	Cancer hospital Chinses academy of medical sciences, shenzhen center	Shenzhen	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of HeBei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Shanxi Cancer hospital	Taiyuan	Shanxi
China	Tangshang people's hospital	Tangshan	Hebei
China	Tianjin Chest Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Tonghua Central Hospital	Tonghua	Jilin
China	Xinjiang Medical University Cancer Hospital	Urumqi	Xinjiang
China	Weifang NO.2 people's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	The first affiliated hospital of wannan medical college	Wuhu	Anhui
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Qinghai university affiliated hospital	Xining	Qinghai
China	The First Affiliated Hospital of Xinxiang Medical College	Xinxiang	Henan
China	The affiliated hospital of xuzhou medical university	Xuzhou	Jiangsu
China	The Second People's Hospital of Yibin City	Yibin	Sichuan
China	General hospital of ningxia medical university	Yinchuan	Ningxia
China	Zhangzhou municipal hospital of fujian province	Zhangzhou	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival(OS)	OS is defined as the time from randomization to death due to any cause.	Through Database Cutoff Date (Up to approximately 39 months)
Primary	Progression-Free Survival(PFS) by investigator(INV)	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	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Progression-Free Survival(PFS) by Blind independent center review(BIRC)	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	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Objective response rate (ORR) was assessed by INV	ORR is the proportion of subjects with CR or PR based on RECIST v1.1	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Disease control rate (DCR) was assessed by INV	Disease control rate (DCR) was assessed based on RECIST V1.1 criteria	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Time to response (TTR) was assessed by INV	The time from the first administration to the date of documented CR or PR	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Duration of response (DOR) was assessed by INV	Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Objective response rate (ORR) was assessed by BIRC	ORR is the proportion of subjects with CR or PR based on RECIST v1.1	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Disease control rate (DCR) was assessed BIRC	Disease control rate (DCR) was assessed based on RECIST V1.1 criteria	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Time to response (TTR) was assessed by BIRC	The time from the first administration to the date of documented CR or PR	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Duration of response (DOR) was assessed by BIRC	Measured from the date of partial or complete response to therapy until the disease progression per RECIST v1.1 criteria	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	The number of subjects experiencing adverse events (AEs)	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Pharmacokinetic	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	Antidrug antibodies (ADA) of AK104	Proportion of subjects who develop detectable anti-drug antibodies (ADAs)	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	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)	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.	Through Database Cutoff Date (Up to approximately 39 months)
Secondary	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)	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.	Through Database Cutoff Date (Up to approximately 39 months)