Clinical trial NCT05922345: Evaluation of the Efficacy and Safety of AL2846 Capsule Combined With TQB2450 Injection Compared to Docetaxel Injection in Advanced Non-small Cell Lung Cancer Patients Who Have Failed With Immunotherapy.
Official title: A Multicenter, Randomized, Double-blind, Parallel-controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of AL2846 Capsules Combined With TQB2450 Injection Compared With Docetaxel Injection in Patients With Advanced Non-small Cell Lung Cancer Who Have Failed With Immunotherapy.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-28
Enrollment: 518
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy of AL2846 capsules in combination with TQB2450 injection or Docetaxel injection in patients with advanced NSCLC who have previously failed immune checkpoint inhibitors (anti-PD-1 monoclonal antibody, anti-PD-L1 monoclonal antibody), regardless of new anti-tumor treatment and early termination of treatment.


Eligibility criteria: Inclusion Criteria:

* The subjects voluntarily joined the study, signed an informed consent form, and had good compliance
* Age: 18-75 years; Eastern Eastern Cooperative Oncology Group performance status (ECOG PS) score: 0-1; BMI ≥ 17 at baseline;
* Patients with histologically or cytologically confirmed inoperable and inoperable locally advanced (stage IIIB/IIIC), metastatic or recurrent (stage IV) nonsmall-cell lung cancer (NSCLC) who cannot receive radical concurrent chemoradiotherapy;
* Failure of platinum-based chemotherapy and immune checkpoint inhibitors for incurable locally advanced or metastatic or recurrent NSCLC;
* Number of lines of prior systemic therapy received for locally advanced or metastatic/recurrent disease that is unresectable/not amenable to radical chemoradiation;
* Confirmed to have at least one measurable lesion according to Response Evaluation Criteria In Solid Tumours（ RECIST 1.1） standard;
* Adequate major organ function;

Exclusion Criteria:

* Patients who Have been diagnosed or currently had other malignant tumors;
* Presence of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, c-ros oncogene 1 (ROS1) fusion and other significant driver gene mutations;
* Factors affecting oral drugs;
* Major surgical treatment, incisional biopsy or obvious traumatic injury and long-term uncured wound or fracture within 28 days before the start of study treatment;
* Hyperactive/venous thrombotic events within 6 months;
* Subjects with any severe and/or uncontrolled disease;
* Previously received other immunotherapy and Research Advance of Small Molecular Targeted Anti-Tumor Agents Tyrosine kinase inhibitors (TKIs);
* According to the investigator's judgment, there are concomitant diseases that seriously endanger the subject's safety or affect the completion of the study, or there are other reasons that are not suitable for the subject;

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From randomization to the time of death from any cause, assessed up to 36 months.
Secondary outcomes:
measure: Progression-free survival (PFS) by investigator assessment
timeFrame: From the date of randomization to the date of first recorded progression or death from any cause, whichever comes first, assessed up to 36 months.
measure: Objective response rate (ORR)
timeFrame: Time from the date of randomization to the first recorded complete remission (CR) or partial remission (PR), assessed up to 36 months.
measure: Disease Control Rate (DCR)
timeFrame: Time from randomization date to CR, PR, or SD or 6 weeks, whichever came first.
measure: Duration of response (DOR)
timeFrame: From the date of first documentation of tumor response to the date of first documentation of disease progression or death due to any cause, whichever occurs first, assessed up to 36 months.
measure: 12-month survival rate (12-month OS rate)
timeFrame: Baseline up to 12-month
measure: Health Questionnaire Form
timeFrame: During the screening period, the second cycle and other even numbered cycles, each cycle is 21 days, assessed up to 36 months.
measure: Effects on subjects' health-related quality of life
timeFrame: During the screening period, the second cycle and other even numbered cycles, each cycle is 21 days, assessed up to 36 months.
measure: Patients with abnormal laboratory inspection indicators
timeFrame: From signing the informed consent form to the 30 days after the last dose.
measure: Adverse event rate
timeFrame: From signing the informed consent form to the 30 days after the last dose.
measure: Occurrence of anti-drug antibody (ADA)
timeFrame: Pre-dose in cycle 1, cycle 2, cycle 5, cycle 9, 90 days after administration, each cycle is 21 days.
measure: Occurrence of neutralizing antibody (Nab)
timeFrame: Pre-dose in cycle 1, cycle 2, cycle 5, cycle 9, 90 days after administration, each cycle is 21 days.
measure: Peak Concentration (Cmax)
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: Trough concentration (Cmin)
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: Peak time
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: Area under the drug time curve (AUC)
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: Clearance
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: Apparent volume of distribution (Vd)
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
measure: The elimination half-life (t1/2)
timeFrame: 60 minutes pre-dose on cycle 1 day 1, cycle 2 day 1, cycle 5 day 1, cycle 9 day 1; 10 minutes post dose on cycle 1 day 1, each cycle is 21 days.
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: Three Gorges Hospital Affiliated to Chongqing University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan City People's Hospital
state: Guangdong
city: Guigang
country: China
facility: Guigang people's hospital
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou people's hospital
state: Guangxi
city: Nanning
country: China
facility: Guangxi Medical University Afiliated Tomor Hospital
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Zunyi
country: China
facility: The Second Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Haikou
country: China
facility: The Second Affiliated Hospital of Hainan Medical College
state: Hainan
city: Haikou
country: China
facility: Hainan Provincial People's Hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Tuberculosis Hospital (Jiamusi Cancer Hospital)
state: Heilongjiang
city: Wuhan
country: China
facility: Tong Ji Hospital Affiliated To Tongji Medical College HUST
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital (HBCH)
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: XuZhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Tenth People'S Hospital
state: Liaoning
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Air Force Medical University
state: Shaanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of the Military Medical University of the PLA Air Force
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Heze
country: China
facility: Heze Municipal Hospital
state: Shandong
city: Jinan
country: China
facility: The Second Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital&Institute
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical Uniwersity
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Changzhi
country: China
facility: Changzhi People'S Hospital
state: Shanxi
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Nanchong
country: China
facility: Affiliated Hospital of North SIchuan Medical College
state: Sichuan
city: Neijiang
country: China
facility: The second people's hospital of neijiang
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: Ürümqi
country: China
facility: Affiliated Tumor Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Enze Medical Center (Group)
state: Zhejiang
Study officials:
References: