Advanced NSCLC resistant to third-generation EGFR-TKI
Conditions
Interventions
Single group 1:Intravenous infusion of BEBT-908
Single group 2:Oral BEBT-109
Combination group :Intravenous drip infusion of BEBT-908 and oral administration of BEBT-109
Sponsors
Hu'nan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years, male or female; 2. Written informed consent must be obtained from the subject or legal representative before any study-specific screening procedure; 3. Locally advanced or metastatic NSCLC, except for squamous cell carcinoma (confirmed by histology or cytology); 4. Carry EGFR-sensitive mutations by genetic testing, including deletion mutations in exon 19 and L858R point mutations in exon 21; 5. Progressors with EGFR-sensitive mutations who have previously received third-generation EGFR-TKI therapy (if enrolled in Cohort 3, they also need to receive at least one platinum-based chemotherapy and progress); 6. At least one measurable lesion that meets RECIST 1.1 criteria. Tumor lesions previously treated with radiotherapy or other local therapy are considered measurable only if progressive disease at the treatment site is clearly documented after completion of therapy; 7. ECOG score 0-2 points, and no decline in performance in the past two weeks; 8. Expected survival of at least 12 weeks; 9. Adequate organ and bone marrow function, defined as follows: (1) ANC >= 1500/mm^3 (1.5 x 10^9/L); (2) Platelets >= 100,000/mm^3 (1.5 x 10^9/L); (3) Hemoglobin >= 9 g/dL(90g/L); (4) ALT or AST = 60 mL/min (according to Cockcroft and Gault formula); 10. All acute toxic reactions of previous anticancer therapy or surgery resolved to baseline severity or NCICTCAE version 5.0 <= grade 1 (except alopecia or other toxicities that, in the opinion of the investigator, pose no safety risk to the patient); 11. Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days before the start of study medication and are willing to use a medically recognized highly effective contraceptive (e.g., intrauterine device, contraceptive pills, or condom) during the study and within 1 month after the administration of study drug.
Exclusion criteria
Exclusion criteria: 1. Combined with any other malignant tumor (except adequately treated basal cell or scaly cell skin cancer or cervical carcinoma in situ); 2. Excessive surgery, chemotherapy, radiation therapy, any investigational drugs or other anticancer therapy before the first dose; 3. Patients received the following treatments within 7 days before the first dose: (1) Drugs known to be potent inhibitors/inducers of CYP3A4/CYP2C8; (2) Drugs known to significantly prolong the QT interval or torsades de pointes (antiarrhythmic drugs such as quinidine, isopropylpyrazine, procainamide, sotalol, etc.); 4. Have received any continuous or intermittent such as PI3K inhibitors, mTOR inhibitors, HDAC inhibitors before entering the group (HDAC inhibitors Cedaramide treatment cannot be excluded); 5. Known history of allergy or suspected allergic symptoms to any component of BEBT-908 and BEBT-109 capsules for injection; 6. At rest, the mean corrected QT interval (QTc) obtained from 3 electrocardiogram (ECG) examinations is > 480 msec (only when the first ECG indicates QTc > 480 msec, retest is required and the mean corrected value is taken for 3 times); a history of long QT syndrome or a confirmed family history of long QT syndrome; a history of clinically significant arrhythmia, or a current use of antiarrhythmic drugs or a defibrillation device implanted for the treatment of ventricular arrhythmias; 7. Uncontrolled electrolyte imbalance, which may affect the effect of QTc prolonging drugs (such as hypocalcemia = grade 2 sustained arrhythmia, any grade of atrial fibrillation, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic cerebral embolism); 9. Clinical routine establishment of venous access site grade 2 phlebitis or more than grade 2 vasculitis; 10. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome or any upper gastrointestinal surgery including gastrectomy; known malabsorption syndrome or other conditions that may impair the absorption of BEBT-109; 11. Clinically significant active infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related diseases; active hepatitis B is defined as: positive hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg), and HBV-DNA >= 2000 IU/mL (equivalent to 10^4 copies/mL). Patients with hepatitis B DNA quantification >= 2000 IU/mL are allowed to be treated with antiviral drugs before screening, and can only be treated when the viral copy is reduced to less than 2000 IU/mL, but patients need to receive continuous anti-hepatitis B virus treatment during the trial); active hepatitis C is defined as HCV-RNA higher than the upper limit of detection; HIV1/2 antibody positive or definite AIDS disease diagnosis certificate; 12. Other serious acute or chronic medical or psychiatric disorders or laboratory abnormalities that may increase the risk of study participation or increase the risk associated with the administration of study drugs, or interfere with the study results, as well as other conditions that the investigato
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR(Objective Response Rate);Pharmacokinetics;Safety and tolerance;DCR(Disease Control Rate);TTR(Time in Therapeutic Range);DOR(Duration of Response);PFS(Progress-Free Survival);OS(Overall Survival); | — |
Countries
China
Contacts
Public ContactQian Changgeng
Guangzhou BeBetter Medicine Technology Co., Ltd.
Outcome results
None listed