Non-small cell lung cancer
Conditions
Interventions
Phase Ib Group A:40mg, continuous administration, once every other day
Phase Ib Group B:The dose to be taken is determined by SMC based on the discussion of available clinical data, and is administered continuously and once every other day
Phase II group:Receive study drug treatment 1 time (fasting) every other day in a dosing cycle every 28 days until disease progression and the investigator judges that continued treatment with study d
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age 18 (including 18) years old or above, gender is not limited; 2. Patients with locally advanced or metastatic NSCLC confirmed by pathological histology and/or cytology; 3. Rare EGFR mutations (tumor tissue biopsy samples), including one or more of L861Q, G719X, S768I, and E709X mutations (excluding other EGFR-sensitive mutations and/or other driver genes), receive previous genetic test results within 2 years, or collect fresh tumor tissue samples or provide previous tumor tissue samples to confirm the EGFR mutation type during the screening period; 4. At least one measurable tumor lesion according to RECIST version 1.1 (tumor lesions located in the area of prior radiotherapy or other locoregional treatment sites, generally not considered measurable lesions, unless the lesion has shown definite progression); 5. ECOG physical strength score 0-1 points; 6. Estimated survival time of more than 3 months; 7. Have adequate organ function: (1) Blood system (no blood transfusion or hematopoietic stimulating factor therapy within 14 days) Absolute neutrophil value (ANC) >=1.5×10^9/L; Platelets (PLT) >=90×10^9/L; Hemoglobin (Hb) > = 90 g/L (2) Liver function total bilirubin (TBIL) 1.5× ULN) > 50 ml/min (calculated according to the Cockcroft-Gault formula) (4) Coagulation function Activated partial thromboplastin time (APTT) = 2, 24-hour urine protein < 1 g 8. Eligible patients (male and female) of childbearing potential must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) with their partner for the duration of the trial and for at least 3 months after the last dose; Female patients of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose of study drug. 9. Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form.
Exclusion criteria
Exclusion criteria: 1. Patients with other primary malignancies (except for basal cell carcinoma of the skin and carcinoma in situ of the cervix that have been cured and have not recurred for 5 years, low-grade prostate cancer with low risk, carcinoma in situ of the lung and carcinoma in situ of the duct of the breast); 2. Received any epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) anti-tumor therapy prior to enrollment (except for Phase Ib Group A, which allows enrollment of up to 3 patients who have received EGFR-TKI therapy before); 3. Received anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 3 weeks before the first use of the study drug, except for the following: Nitrosourea or mitomycin C within 6 weeks before the first use of the study drug; Oral fluorouracil and small molecule targeted drugs are within 5 half-lives or 2 weeks of the first use of the study drug (whichever is shorter); Traditional Chinese medicine (including proprietary Chinese medicine and herbal medicine) with anti-tumor indications within 2 weeks before the first use of the study drug; 4. Received other unmarketed clinical investigational drugs or treatments within 4 weeks prior to the first use of the investigational drug; 5. Have undergone major organ surgery (excluding needle biopsy) or have significant trauma within 4 weeks prior to the first use of study drug, or need to undergo elective surgery during the trial; 6. Received systemic treatment with glucocorticoids (prednisone > 10mg/day or equivalent doses) or other immunosuppressants within 14 days prior to the first use of the study drug; The following are excluded: treatment with topical, ocular, intra-articular cavity, intranasal, and inhaled corticosteroids; short-term prophylaxis with glucocorticoids (e.g., prevention of contrast allergy); 7. Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past; 8. The adverse reactions of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade evaluation 1000IU/ml or the lower limit of detection at the research center [only if the lower limit of detection at the center is higher than 1000IU/ml]); Active hepatitis C (patients with positive HCV antibodies but lower limit of HCV-RNA detection =grade 3 interstitial pneumonia or pulmonary disease that may interfere with drug-related pulmonary toxicity (such as COPD, autoimmune disease involving the lungs); 14. Have a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: (1) Have severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requirin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib: RP2D (recommended dose for Phase II clinical trial);Phase II: Objective Response Rate (ORR);Phase Ib: occurrence and frequency of AEs, SAEs; | — |
Countries
China
Contacts
Public ContactZhengbo Song
Zhejiang Cancer Hospital
Outcome results
None listed