Non-small cell lung cancer
Conditions
Interventions
treatment group:JMKX001899monotherapy
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects should be fully informed and obtain written informed consent before the screening procedure; 2. Male or female aged >= 18; 3. Advanced solid tumor confirmed by histology or cytology after gene mutation detection and confirmed as KRAS (G12C) mutation. For Phase Ib and Phase II, mutations will be confirmed by central laboratory testing before enrollment; 1) Phase Ia subjects (solid tumors) were patients who failed to receive standard treatment or refused to receive standard treatment or had no standard treatment or could not benefit from standard treatment according to the judgment of the researcher; 2) Phase Ib and Phase II subjects (NSCLC) must have previously received platinum-containing chemotherapy or targeted therapy (such as EGFR, ALK and ROS1) or anti-PD1/anti-PD-L1 immunotherapy before disease progression. Subjects should not receive more than 3 lines of treatment in the past. 4. According to RECIST version 1.1, there should be at least one measurable lesion displayed by CT or MRI; 5. The patient's ECOG physical state is 0-1 (Phase Ia); 0-2 (Phase Ib and II) 6. The patient has sufficient organ function, which is defined as: A. Blood system: absolute neutrophil count (ANC) >= 1.5 × 10^9/L, platelet >= 80 × 10^9/L, hemoglobin >= 90 g/L; B. Cardiac function: left ventricular ejection fraction (LVEF) >= 50%; C. Liver function: total bilirubin = 50mL/min (according to Cockcroft and Gault formula); E. Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) or international standardized ratio (INR) (if undergoing preventive anticoagulation treatment) <= 1.5 times ULN; 7. The expected survival time is more than 3 months; 8. The test results of serum pregnancy test conducted by women of reproductive age (including premenopausal and postmenopausal women within 2 years) within 7 days before the first study drug administration must be negative and must be non-lactating, And the fertile male (including the female spouse of male subjects of childbearing age) and female subjects must agree to voluntarily maintain abstinence or take medically approved effective non-drug contraceptive measures (such as intrauterine devices or condoms) within at least 6 months from screening to the last administration.
Exclusion criteria
Exclusion criteria: 1. Those who are allergic to the main ingredients and excipients of JMKX001899 tablets, or have allergic constitution; 2. Previously received KRAS G12C mutation specific inhibitor treatment; 3. Patients with symptomatic brain metastasis or brain metastasis requiring treatment, meningeal metastasis; 4. Patients with other malignant tumors at the same time (except skin basal cell carcinoma and cervical carcinoma in situ which have not recurred within 5 years); 5. Human immunodeficiency virus (HIV) test positive or hepatitis B surface antigen (HBV) test positive or hepatitis C virus (HCV) antibody test positive; 6. The patient has not recovered from the AE induced by previous anti-tumor therapy to <= 1 or baseline level (excluding alopecia and <= 2 neuropathy); 7. The patient is currently participating in and receiving research treatment or has participated in clinical trials within 28 days before the first administration; 8. During the study period, other anti-tumor drugs are also required for concomitant treatment; 9. Have received monoclonal antibody or other immunosuppressive anti-tumor treatment within 4 weeks before the first administration; Systematic chemotherapy, radiotherapy (except palliative radiotherapy for targeted bone metastasis), targeted therapy, or Chinese herbal anti-tumor therapy were received within 2 weeks before the first administration or within the half-life of 5 known drugs (whichever is longer); 10. Drugs that may affect the metabolism of this product, such as CYP3A4 strong inhibitors (clarithromycin, protease inhibitors, triazole antifungal drugs, etc.), CYP3A4 strong inducers (rifampicin, carbamazepine, phenytoin, etc.) or drugs with narrow therapeutic index for CYP3A4 sensitive substrate, have been used 14 days before the first administration or within 5 half-lives (whichever is longer); Or grapefruit or products containing grapefruit that have not been reviewed and approved by the investigator and/or medical inspector within 7 days before the first administration. 11. Those who have received live vaccine within 30 days before the first administration; 12. Those who have difficulty swallowing, suffer from malabsorption syndrome, other diseases that cannot absorb drugs through the intestine or affect the absorption of JMKX001899; 13. There are other serious diseases, including liver disease, kidney disease, nerve/mental disease, endocrine system disease, blood system disease, immune system disease, and the researcher's judgment will affect the participation in this study; 14. Pulmonary interstitial disease, pulmonary interstitial fibrosis or previous history of drug-induced interstitial pneumonia (excluding pneumonia caused by radiotherapy); 15. Have a history or evidence of cardiovascular (CV) risk, including any of the following: A history of serious uncontrolled arrhythmia or clinically significant ECG abnormalities within 6 months before screening, including second degree (type II) or third degree atrioventricular block; Cardiomyopathy and myocardial infarction occurred within 6 months before screening; Acute coronary syndrome (including unstable angina pectoris), coronary angioplasty, stent implantation or bypass grafting were accepted within 6 months before enrollment; Congestive heart failure (Class III or IV) as defined by the New York Heart Association Functional Classification System (NYHA); 16. During the screening period, 12-lead electrocardiogram (ECG) measurement was conducted in the research cen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicity;Maximum tolerated dose;Recommended Phase II dose;Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Overall survival;Time to response;Duration of response;Disease control rate;Clinical benefit response; | — |
Countries
CHINA
Contacts
Public ContactZhang Jian
Outcome results
None listed