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

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)

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%.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic NSCLC
• Intervention / Treatment: Drug: AK104; Drug: carboplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 642
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhifang Yao, M.D.; Phone Number: +86-0760-89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233099
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital
    • Wuhu, Anhui, China, 241001
      • The First Affiliated Hospital of Wannan Medical College
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 101149
      • Beijing Chest Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Beijing, Beijing, China, 100039
      • The Fifth Medical Center of the Chinese People's Liberation Army General Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Zhangzhou, Fujian, China, 363099
      • Zhangzhou Municipal Hospital of Fujian Province
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Gansu Provincial Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510095
      • Affiliated Cancer Hospital and institute of Guangzhou Medical University
    • Shenzhen, Guangdong, China, 518172
      • Cancer hospital Chinses academy of medical sciences， shenzhen center
  • Hainan
    • Haikou, Hainan, China, 570312
      • Hainan Cancer Hospital
  • Hebei
    • Baoding, Hebei, China, 050031
      • Affiliated Hospital of Hebei University
    • Hengshui, Hebei, China, 053099
      • The second people's hospital of Hengshui
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050004
      • The Second Hospital of Hebei Medical University
    • Tangshan, Hebei, China, 063001
      • Tangshang people's hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
    • Jiamusi, Heilongjiang, China, 154007
      • Jiamusi Tuberculosis Prevention and Control Hospital (Jiamusi Cancer Hospital)
    • Qiqihar, Heilongjiang, China, 161005
      • The First Hospital of Qiqihar
  • Henan
    • Luoyang, Henan, China, 450052
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Nanyang, Henan, China, 473005
      • Nanyang Central Hospital
    • Xinxiang, Henan, China, 45310
      • The First Affiliated Hospital of Xinxiang Medical College
    • Zhengzhou, Henan, China, 450052
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410012
      • The Second Xiangya Hospital, Central South University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221799
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • First Affiliated Hospital of Gannan Medical College
    • Nanchang, Jiangxi, China, 330006
      • First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130061
      • The first hospital of Jilin Universit
    • Tonghua, Jilin, China, 134099
      • Tonghua Central Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Liaoning Cancer Hospital
    • Shenyang, Liaoning, China, 110002
      • The First Hospital of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750003
      • General Hospital of Ningxia Medical University
  • Qinghai
    • Xining, Qinghai, China, 810012
      • Qinghai University Affiliated Hospital
  • Shandong
    • Binzhou, Shandong, China, 256603
      • Binzhou Medical University Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University
    • Weifang, Shandong, China, 261041
      • Weifang NO.2 People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University
  • Shanxi
    • Changzhi, Shanxi, China, 046099
      • Changzhi People's Hospital
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Cancer Hospital
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
    • Mianyang, Sichuan, China, 621099
      • Mianyang Central Hospital
    • Yibin, Sichuan, China, 644000
      • The Second People's Hospital of Yibin City
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
    • Tianjin, Tianjin, China, 300222
      • Tianjin Chest Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Xinjiang Medical University Cancer Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital /the Third Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine (Fahzu)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 arm	Drug: AK104; AK104 IV, q3w; Drug: carboplatin; carboplatin IV, q3w; Drug: Pemetrexed; Pemetrexed IV, q3w (for Nonsquamous NSCLC); Drug: Paclitaxel; Paclitaxel IV, q3w (for squamous NSCLC)
Active Comparator: Tislelizumab arm	Drug: carboplatin; carboplatin IV, q3w; Drug: Pemetrexed; Pemetrexed IV, q3w (for Nonsquamous NSCLC); Drug: Paclitaxel; Paclitaxel IV, q3w (for squamous NSCLC); Drug: Tislelizumab; Tislelizumab IV, q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Antidrug antibodies (ADA) of AK104	Proportion of subjects who develop detectable anti-drug antibodies (ADAs)	Through Database Cutoff Date (Up to approximately 39 months)
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)
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)

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Jie Wang, M.D., Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Principal Investigator: Qingming Wang, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 14, 2023
• Primary Completion (Estimated): August 5, 2025
• Study Completion (Estimated): November 28, 2026

Study Registration Dates

• First Submitted: August 3, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed; Tislelizumab
• Other Study ID Numbers: AK104-307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No