Clinical trial NCT03972189: Safety and Efficacy Study of TQ-B3101 in Patients With ROS1-positive Non-Small Cell Lung Cancer (NSCLC)
Official title: Phase II, Open Label, Single Arm Study of the Efficacy and Safety of TQ-B3101 in Patients With ROS1-positive Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: ROS1-positive Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess efficacy and safety of oral TQ-B3101 administered to patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that confirmed ROS1 positive gene mutation.


Eligibility criteria: Inclusion Criteria:

1.18 years and older. 2.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy ≥ 3 months.

3.Understood and Signed an informed consent form. 4.Histologically or cytologically confirmed locally advanced or metastatic NSCLC .

5.Subjects in the screening period should provide a written report of ROS1 positive, or tumor histological specimens obtained at the time of diagnosis/post before enrollment are sent to the central laboratory to confirm ROS1 positive.

6. Had received no more than two chemotherapy regimens. 7.At least 1 measurable tumor lesion other than brain lesions within 28 days before first dose based on RECIST 1.1.

8.The main organs function are normally, the following criteria are met:

1. routine blood tests（no blood transfusion and blood products within 14 days）：hemoglobin（Hb）≥90g/L；absolute neutrophil count（ANC）≥1.5×109/L； platelets（PLT）≥100×109/L.
2. Blood biochemical examination: alanine transaminase（ALT）and aspartate aminotransferase（AST）≤2.5×upper limit of normal (ULN)（when the liver is invaded, ALT, and AST ≤5× upper limit of normal (ULN) ）； total bilirubin (TBIL)≤1.5×upper limit of normal (ULN)；Serum creatinine ≤ 1.5 × upper limit of normal (ULN); or creatinine clearance calculated ≥ 50ml / min (calculated according to Cockcroft-Gault formula);
3. left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥ 50%.

   9.Women must meet one of the following conditions:has undergone surgical sterilization;have been menopausal at least 1 year;have fertility, the following conditions must be met;Serum pregnancy test results were negative; throughout the study period to 6 months after the last dose, agreed to adopt an approved method of contraception (for example: oral contraception, injection contraception or implanted, barrier-effect Contraceptive methods, spermicides and condoms, or intrauterine devices).Men must meet one of the following conditions:has surgical sterilization;an approved method of contraception must be used throughout the study period and 6 months after the last dose.

   Exclusion Criteria:
   1. Has any known endothelial growth factor receptor (EGFR) positive mutation.
   2. Prior therapy with crizotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or any other ROS1 inhibitor.
   3. Has multiple factors affecting oral medication, such as inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.
   4. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of cured carcinoma in situ of the cervix、 non-melanoma skin cancers and superficial bladder tumors.
   5. Has a history of hypertensive crisis, hypertensive encephalopathy; or uncontrolled hypertension.
   6. Has clinically significant, uncontrolled cardio-cerebral vascular disease.
   7. Has major surgery and anti-tumor treatment before two weeks of treatment and participated in other drug clinical trials within four weeks.
   8. Has known central nervous system metastasis and/or spinal cord compression, cancerous meningitis, and pia mater disease.
   9. Has in screening period confirmed HCV positive, HIV positive, active syphilis positive, or HBsAg positive, HBV DNA titers \>500 copies/ml and stable time \<14 days after symptomatic treatment,or has a history of stem cells and organ transplantation.
   10. Has history of psychotropic substance abuse that unable to abstain from or mental disorder.
   11. According to the judgement of the researchers, there are other factors that may lead to the termination of the study.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: up to approximately 20 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: up to approximately 20 months
measure: Disease control rate (DCR)
timeFrame: up to approximately 20 months
measure: Progression-free survival (PFS)
timeFrame: up to approximately 20 months
measure: Overall survival (OS)
timeFrame: up to approximately 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui chest hospital
state: Anhui
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Tumor hospital, Chinese academy of medical sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Tumor Hospital
state: Fujian
city: Guangzhou
country: China
facility: Affiliated tumor hospital of sun yat-sen university
state: Guangdong
city: Guangzhou
country: China
facility: The first affiliated hospital of guangdong pharmaceutical university
state: Guangdong
city: Guangzhou
country: China
facility: The first affiliated hospital of guangzhou medical college
state: Guangdong
city: Ha'erbin
country: China
facility: Affiliated tumor hospital of Harbin medical university
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Changsha
country: China
facility: Hunan provincial tumor hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Centre-south University
state: Hunan
city: Changchun
country: China
facility: Second hospital of jilin university
state: Jilin
city: Dalian
country: China
facility: The second affiliated hospital of dalian medical university
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Linyi
country: China
facility: Linyi tumor hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao University Medical College Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Jiaotong University Affiliated Chest Hospital
state: Shanghai
city: Xi'an
country: China
facility: The first affiliated hospital of xi 'an jiaotong university
state: Shanxi
city: Tianjin
country: China
facility: Tianjin tumor hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital School of Medical,Zhejiang University
state: Zhejiang
Study officials:
References: