MTAP homozygous deletion in locally advanced or metastatic NSCLC.
Conditions
Interventions
Ia Group:Two dose levels of GTA182 tablets were prespecified, and the dose-escalation study was conducted using the 3+3 design principle.
Ib group:GTA182 tablets at the recommended dose + Vumetostat Mesylate Tablets
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The subjects must have given informed consent to this study before the trial and voluntarily sign the written ICF, agreeing to abide by the research protocol; 2. For male or female subjects aged 18 or above at the time of signing the ICF; 3. Expected lifespan > 3 months; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 5. Able to provide archived and/or baseline tumor tissue samples to meet the minimum tissue requirements for central laboratory MTAP homozygous deletion detection or able to provide a researcher-approved previous NGS or immunohistochemistry (IHC) report confirming MTAP homozygous deletion; 6. Locally advanced or metastatic NSCLC diagnosed by histological or cytological means; 7. Previous treatment history must meet the following requirements: failure of previous first-generation, second-generation, or third-generation EGFR-TKIs treatment, or failure of first-generation or second-generation EGFR-TKIs treatment and negative EGFR T790M; 8. According to the RECIST V1.1 standard, at least one measurable lesion; 9. Within 7 days before the first administration, based on the following laboratory tests, the subjects were judged to have good bone marrow function, heart, lung, liver, and kidney functions and coagulation function (the first administration of the study drug is not allowed to receive blood transfusion or other growth factor supportive treatment within 14 days): • Bone marrow function: ANC >= 1.5×10^9/L, platelet count >= 100×10^9/L and hemoglobin >= 90g/L; • Liver: total bilirubin (TBIL) = 30g/L; • Kidney: serum creatinine concentration = 1.5×ULN, the estimated creatinine clearance rate must be >= 50 mL/min (according to the Cockroft-Gault formula); • Coagulation (without anticoagulation treatment): activated partial thromboplastin time (APTT) = 60 years old, if they have stopped menstruation for 12 months or more before the planned enrollment date and there are no other medical causes, it is considered that the woman has reached menopause. For women = 4 weeks Radiotherapy >= 4 weeks (if the radiotherapy is palliative stereotactic radiotherapy not
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women; 2. Individuals who have experienced toxic side effects from previous anti-tumor treatments (including concurrent radiotherapy and chemotherapy or surgical treatment) and whose toxicity has not yet recovered to a CTCAE V5.0 grade assessment of 100 beats per minute, significant ventricular arrhythmias (such as ventricular tachycardia) or advanced atrioventricular conduction block (such as second-degree atrioventricular conduction block Mobitz II or third-degree atrioventricular conduction block); • Had baseline QT/QTc interval prolongation (QTcF: male >450 ms, female >470 ms) (for both male and female, QTcF is calculated using the Fridericia correction formula QTcF = QT/RR^0.33); • Had baseline echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) =180 mmHg, diastolic blood pressure >=110 mmHg) or diabetes (glycated hemoglobin >=9.0%); • Had a history of cardiac surgery, such as angioplasty or coronary artery bypass grafting; • Had severe aortic valve stenosis; • Had clinically significant active infections that require systemic antibiotics, antiviral or antifungal treatment; • Had a large amount of serous cavity effusion, or poorly controlled serous cavity effusion (defined as: carrying a drainage tube or having a drainage frequency of more than once per week); • Had evidence of central nervous system hemorrhage on baseline MRI or CT scan (stable insufficient for 3 months after postoperative asymptomatic grade 1 hemorrhage); • Had uncontrolled seizures; • Had thromboembolism (such as lower extremity venous thrombosis) within 3 months before the first administration, which persisted and was judged by the investigator to have a significant safety risk; • Had severe pulmonary disease, including but not limited to pulmonary embolism, severe asthma, chronic obstructive pulmonary disease (COPD), restrictive lung disease, or active pneumonia or interstitial pneumonia or systemic steroid treatment-induced pneumonia, and had severely impaired lung function as indicated by pulmonary function tests; 6. Clinically unstable brain metastases, defined as having symptoms that require steroid, diuretic, or anticonvulsant treatment, or radiotherapy to control related symptoms; 14.having meningeal metastases, brainstem metastases, spinal cord metastases and/or compression. Subjects with asymptomatic brain metastases after treatment, who do not require steroid or diuretic treatment, and who h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of dose-limiting toxicities (DLTs);Incidence and severity of TEAEs, TRAEs, and SAEs; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic characteristics;ORR,DoR, DCR and PFS, TTR;Biomarkers associated with GTA182 efficacy - SDMA;Biomarker Correlates with GTA182 Efficacy – ctDNA;Biomarker-Gene Mutation Profiling in Tissue Samples Associated with GTA182 Efficacy; | — |
Countries
China
Contacts
Public ContactLu Shun
Shanghai Chest Hospital
Outcome results
None listed