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

Non Small Cell Lung Cancer Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06300177
• Other study ID #: D1553-III-01
• Status: Recruiting
• Phase: Phase 3
• Start date: March 28, 2024
• Est. completion date: December 2027

Study information

• Verified date: March 2024
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Shun Lu, Doctor
• Phone: 13601813062
• Email: shun_lu[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 522
• Est. completion date: December 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• D-1553 Tablet
D-1553 is a KRAS inhibitor.
• Docetaxel injection
Docetaxel, is an anti-tumor drug, significantly reduces the number of free tubules by promoting tubule polymerization into stable microtubules and inhibiting their depolymerization.

Locations

Country	Name	City	State
China	Anyang Tumor Hospital	Anyang	Henan
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chest Hospital,Capital Medical University	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The Fifth medical center of Chinese PLA General Hospital	Beijing	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital Of Central South University	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Changzhi People's Hospital	Changzhi	Shanxi
China	The first people's hospital of Changzhou	Changzhou	Jiangsu
China	The Affiliated Hospital of Chengde Medical College	Chengde	Hebei
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Army Medical Center	Chongqing	Chongqing
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Chongqing University Three Gorges Hospital	Chongqing	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Southwest hospital of AMU	Chongqing	Chongqing
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital Of Fujian Medical University	Fuzhou	Fujian
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guilin Medical College	Guilin	Guangxi
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Hainan Provincial People's Hospital	Haikou	Hainan
China	The First Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Affiliated Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Province Hospital	Hefei	Anhui
China	Jiamusi Tuberculosis Hospital(Jiamusi Cancer Hospital)	Jiamusi	Heilongjiang
China	Shandong Cancer Hospitai	Jinan	Shandong
China	Jining First People's Hospital	Jining	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Gansu Provincial Cancer Hospital	Lanzhou	Gansu
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	The Affiliated Hospital Of Southwest Medical Unerversity	Luzhou	Sichuan
China	Mianyang Central Hospital	Mianyang	Sichuan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	General Hospital of eastern theater command	Nanjing	Jiangsu
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Nanyang second general hospital	Nanyang	Henan
China	The First affiliated Hospital of Nanyang Medical College	Nanyang	Henan
China	The second people's hospital of neijiang	Neijiang	Sichuan
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Ruijin Hospital, Shanghai Jiaotong University School Of Medicine	Shanghai	Shanghai
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Shengjing hospital of China medical university	Shenyang	Liaoning
China	The First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Affiliated Hospital of Shandong First Medical University	Tai'an	Shandong
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Tangshan People's Hospital	Tangshan	Hebei
China	Tianjin medical University cancer	Tianjin	Tianjin
China	The Affiliated Tumor Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Weifang people's Hospital	Weifang	Shandong
China	Weihai Municipal Hospital	Weihai	Shandong
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei
China	Zhongnan hospital of Wuhan University	Wuhan	Hubei
China	Jiangyin People's Hospital	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xi'An JiaoTong University	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	The Second Affiliated Hospital of Air Force Medical University	Xian	Shanxi
China	The First Affiliated Hospital Of Xinxiang Medical Unerversity	Xinxiang	Henan
China	Xuchang Central Hospital	Xuchang	Henan
China	The Affiliated Hospital Of XuZhou Medical University	Xuzhou	Jiangsu
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Yulin First People's Hospital	Yulin	Guangxi
China	The Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Provincial People's Hospita	Zhengzhou	Henan
China	The First Affiliated Hospital Zhejiang University School of Medicine	Zhengzhou	Henan
China	The Second Affiliated Hospital of Zunyi Medical University	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Time from subject randomization (first treatment) to first disease progression or death from any cause, whichever occurred first, was assessed by an independent Review Committee (IRC) per Response evaluation criteria in solid tumors (RECIST) 1.1.	Baseline up to 3 years
Secondary	Overall survival (OS)	From randomization to the time of death from any cause.	Baseline up to 3 years
Secondary	Objective mitigation rate (ORR)	According to RECIST 1.1 criteria, proportion of patients with confirmed tumor volume reduction to pre-specified values and maintained minimum requirements; , namely the proportion of patients with complete response (CR) and partial response (PR).	Baseline up to 3 years
Secondary	Duration of Response (DOR)	From the time of tumor first evaluated as complete or partial response to the time of first disease progression or death from various causes.	Baseline up to 3 years
Secondary	Disease control rate (DCR)	According to RECIST 1.1 criteria, proportion of patients with confirmed tumor volume reduction to pre-specified values and maintained minimum requirements; , namely the proportion of patients with CR, PR and stable disease (SD).	Baseline up to 3 years
Secondary	Time to response (TTR)	Time from patient randomization (first treatment) to first response per RECIST 1.1 criteria	Baseline up to 3 years
Secondary	Patient-reported outcome (PRO)	Reports of their health status directly from patients	Baseline up to 3 years
Secondary	Abnormal laboratory test indicators	The occurrence of laboratory test indicators exceed the normal range	From the subject signed the informed consent form to 30 days after the last dose
Secondary	Adverse event rate	The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs)	From the subject signed the informed consent form to 30 days after the last dose
Secondary	Time to Maximum Plasma Concentration (Tmax)	Time to maximum plasma concentration after dosing	Pre-dose and 2 hours after D1553 administration on Day 1 of cycle 1 and cycle 3. Each cycle is 21 days.
Secondary	Half life (t1/2)	Time required for plasma concentrations to drop by half	Pre-dose and 2 hours after D1553 administration on Day 1 of cycle 1 and cycle 3. Each cycle is 21 days.