Clinical trial NCT06300177: D-1553 Tablet Versus Docetaxel Injection for KRAS G12C Mutation-positive Locally Advanced or Metastatic Non-small Cell Lung Cancer After Prior Standard Therapy Failure
Official title: A Randomized, Controlled, Double-blind, Double-simulated, Multicenter Phase III Clinical Study Evaluating D-1553 Tablet Versus Docetaxel Injection for KRAS G12C Mutation-positive Locally Advanced or Metastatic Non-small Cell Lung Cancer After Prior Standard Therapy Failure.
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: 2024-03-08
Enrollment: 522
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: The purpose of this project is to evaluate progression-free survival (PFS) of D-1553 Tablet versus Docetaxel Injection in subjects with prior standard therapy failure kirsten rat sarcoma viral oncogene (KRAS) G12C mutation positive locally advanced or metastatic non small cell lung cancer (NSCLC), progression-free survival (PFS) as assessed by the Independent Review Committee (IRC) based on RECIST 1.1 was used as the primary endpoint.


Eligibility criteria: Inclusion Criteria:

* Voluntary participation in the study and sign of written informed consent after full informed consent, willing and able to comply with the study procedures and requirements specified in the protocol;
* Age greater than or equal to 18 years old; male and female; eastern cooperative oncology group performance status (ECOG) score 0-1; expected survival period greater than or equal to 3 months;
* Pathologically confirmed locally advanced, unresectable and / or metastatic non-small cell lung cancer (stage III b / III c / IV of american joint committee on cancer (AJCC) 8th);
* Subjects must provide adequate and qualified tumor tissue specimens (surgical resection samples or puncture / biopsy tissue samples within 2 years prior to screening) for confirmation of the KRAS G12C mutation in the central laboratory;
* Disease progression or toxicity after previous treatment with first-line anti-PD-1 / PD-L1 and platinum-containing chemotherapy is not tolerated.Subjects who have clear medical reasons and can not tolerate anti-PD-1 / PD-L1 therapy or platinum-containing chemotherapy;
* Having at least one target lesion according to RECIST 1.1;
* Good function of the major organs;
* Female subjects of childbearing age should agree that contraception must be used during the study and within 6 months after the end of the study; the serum pregnancy test is negative within 7 days before study enrollment and must be non-lactating subjects; male subjects should agree that contraception must be used during the study and within 6 months after the end of the study period.

Exclusion Criteria:

* Treatment with a KRAS G12C mutation inhibitor or docetaxel at any previous time;
* NSCLC with mutations of other driver genes;
* Symptomatic or progressive aggravation of central nervous system metastasis or cancerous meningitis. Subjects with a history of brain metastasis may be considered to be selected if they are clinically stable;
* Patients with a previous history of epilepsy；presence of superior vena cava syndrome;
* Cardiovascular system meets any condition:

  1. New York Heart Association (NYHA) Heart Function Grade II and above congestive heart failure;
  2. Severe cardiac arrhythmias requiring medical treatment;
  3. Acute myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass surgery within 6 months prior to enrollment;
  4. Left ventricular ejection fraction (LVEF) \<50%;
  5. QT interval (QTcF) at prolonged;
  6. Hypertension that is not effectively controlled;
* Subjects with stroke or other severe cerebrovascular disease within 6 months before enrollment;
* History of deep vein thrombosis or any other serious thromboembolism within 3 months prior to enrollment;
* History of interstitial lung disease, radiation pneumonitis, and immune-associated pneumonia previously treated with steroids, Or active non-infectious pneumonia with interstitial lung disease, radiation pneumonia, and immune-related pneumonia during the screening period, Presence of active tuberculosis, pneumoconiosis or grade 2 other type of pneumonia, or pulmonary function tests confirming severely impaired pulmonary function;
* Severe bone damage due to tumor bone metastasis may occur at present or after randomization;
* Active or uncontrolled serious infection (≥grade 2 infection of common toxicity criteria for adverse events (CTC AE)) or fever of unknown origin \> 38.5°C;
* The third space effusion (including pleural effusion, abdominal effusion or pericardial effusion), poor clinical control or the need for local symptomatic treatment such as puncture and drainage;
* Known impaired gastrointestinal (GI) function or known GI diseases that may significantly affect the absorption or metabolism of oral drugs.

Previous history of major surgery in the digestive tract (esophagus, gastrointestinal tract) that may alter the absorption or inability to swallow drugs in the study treatment;

* Toxicity of previous antitumor therapy, except alopecia, pigmentation, clinically insignificant laboratory abnormalities) has not recovered to grade 1, and peripheral nerve toxicity has not recovered to grade 2 ( CTCAE v5.0);
* Human immunodeficiency virus (HIV) antibody positive, liver cirrhosis or active viral hepatitis;
* Active syphilis;
* Patients with renal failure requiring hemodialysis or peritoneal dialysis;
* Poor diabetes control \[fasting blood glucose (FBG)\> 10 mmol/L\];
* Previous history of organ transplantation or readiness to undergo organ transplantation;
* Weight of \<40 kg and BMI of \<18.5 kg/m2, or weight loss of\> 5% within 3 months before enrollment;
* Major surgical treatment or significant traumatic injury within 4 weeks prior to the first dose of this study;
* Receiving palliative radiotherapy with local lesions within 2 weeks before the first dose of this study;
* Pregnant or lactating subjects;
* With the combination of other primary malignancies
* Serious mental or mental illness or history of substance abuse or serious alcohol abuse;
* Known allergy to the investigational medicinal product or any ingredient in the formulation;
* Any other significant clinical abnormality or disease that the investigator considers poses a risk to subject safety or interferes with the medication and evaluation of the clinical study.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Baseline up to 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Baseline up to 3 years
measure: Objective mitigation rate (ORR)
timeFrame: Baseline up to 3 years
measure: Duration of Response (DOR)
timeFrame: Baseline up to 3 years
measure: Disease control rate (DCR)
timeFrame: Baseline up to 3 years
measure: Time to response (TTR)
timeFrame: Baseline up to 3 years
measure: Patient-reported outcome (PRO)
timeFrame: Baseline up to 3 years
measure: Abnormal laboratory test indicators
timeFrame: From the subject signed the informed consent form to 30 days after the last dose
measure: Adverse event rate
timeFrame: From the subject signed the informed consent form to 30 days after the last dose
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Pre-dose and 2 hours after D1553 administration on Day 1 of cycle 1 and cycle 3. Each cycle is 21 days.
measure: Half life (t1/2)
timeFrame: Pre-dose and 2 hours after D1553 administration on Day 1 of cycle 1 and cycle 3. Each cycle is 21 days.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Province Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: The Fifth medical center of Chinese PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The Southwest hospital of AMU
state: Chongqing
city: Chongqing
country: China
facility: Army Medical Center
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: The First Affiliated Hospital Of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fujian 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: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Zhanjiang
country: China
facility: The Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical College
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Yulin
country: China
facility: Yulin First People's 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: Hainan Provincial People's Hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Chengde
country: China
facility: The Affiliated Hospital of Chengde Medical College
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)
state: Heilongjiang
city: Anyang
country: China
facility: Anyang Tumor Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang second general hospital
state: Henan
city: Nanyang
country: China
facility: The First affiliated Hospital of Nanyang Medical College
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital Of Xinxiang Medical Unerversity
state: Henan
city: Xuchang
country: China
facility: Xuchang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School of Medicine
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospita
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan hospital of Wuhan University
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: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changzhou
country: China
facility: The first people's hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: General Hospital of eastern theater command
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Jiangyin People's 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: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing hospital of China medical university
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospitai
state: Shandong
city: Jining
country: China
facility: Jining First People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Tai'an
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
state: Shandong
city: Weifang
country: China
facility: Weifang people's Hospital
state: Shandong
city: Weihai
country: China
facility: Weihai Municipal Hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'An JiaoTong University
state: Shanxi
city: Xian
country: China
facility: The Second Affiliated Hospital of Air Force Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital Of Southwest Medical Unerversity
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
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
state: Tianjin
city: Urumqi
country: China
facility: The 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 Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: