Non-small cell lung cancer
Conditions
Interventions
Experimental Group:PLB1004 capsules
Control Group:Pemetrexed, carboplatin, cisplatin, sintilimab
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Ability to understand and willingness to sign a written informed consent document. 2. Aged at least 18 years old. 3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV). 4. Tumor tissue is positive for EGFR Ex20ins as documentally confirmed by next-generation sequencing (NGS) testing or written confirmation of PCR testing by a local laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP), or a central laboratory designated by the sponsor by a tertiary A hospital or with Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP) accreditation (or other equivalent accreditation). 5. At least one measurable lesion as defined by RECISTV1.1(Brain lesions were not included in measurable target lesions). 6. ECOG performance status 0 to 1. 7. Life expectancy is not less than 12 weeks. 8. No previous systemic treatment for locally advanced or metastatic non-squamous cell cancer NSCLC. Note: Subjects are allowed to receive neoadjuvant/adjuvant therapy as long as the relevant therapy has ended at least 6 months before the disease is diagnosed as locally progressive or metastatic tumors. 9. Normal function of major organs, laboratory test results within 7 days prior to the first dose must meet the following requirements:(1) Routine blood test: neutrophil >= 1.5×10^9/L, platelet >= 100×10^9/L, hemoglobin >= 90 g/L, and no blood components or cell growth factor therapy within 14 days before the examination;(2)Liver function: serum albumin (ALB) >= 30 g/L, and no infusion of albumin preparation within 14 days before the examination corrected the treatment; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 50 mL/min, and creatinine clearance was calculated using the Cockcroft-Gault formula (table 15); (4)Coagulation function: activated partial thromboplastin time, international normalized ratio, prothrombin time<=1.5×ULN; 5) Serum amylase <= 1.5× ULN, serum lipase <= 1.5× ULN. 10. Males and females of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of study drug (see Appendix 2 for details). Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to the first dose of study drug.
Exclusion criteria
Exclusion criteria: 1. Have one of the following previous anti-tumor treatments: prior to the first dose of PLB1004. a) Any anti-EGFR TKI for the EGFR ex20ins mutation; b) Received Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drugReceived Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drug; c) required administration of the multidrug and toxin efflux protein (MATE) transporter substrate metformin within 1 week before and during the first study drug administration; d)Strong inhibitors or strong inducers of the cytochrome P450 3A4 enzyme (CYP3A4) were required within 1 week before and during the study; e) required immunosuppressive medication within 2 weeks before or during the first dose of study drug; f) Major surgery within 4 weeks prior to starting PLB1004 or who have not recovered from side effects of such procedure except for the biopsy of Thoracoscopy and the clinical test of Mediastinoscopy could <= 7 days prior to starting PLB1004; g) Radiotherapy to lung fields and whole-brain fields <=4 weeks prior to starting PLB1004. For all other anatomic sites, radiotherapy <=2 weeks prior to starting PLB1004 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions is not included. 2. With concurrent presence of the following EGFR mutation types: Exon19del, L858R, T790M, G719X, S768I, or L861Q. 3. Patients with spinal cord compression, brain membrane metastasis and symptomatic central nervous system (CNS), who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study manage CNS symptoms. 4. The investigator assesses the presence of uncontrolled third-space fluid accumulation, including but not limited to pleural effusion, pericardial effusion, or peritoneal effusion. 5. Before randomization, patients did not recover from any toxicity and/or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage. 6. Did not recover from any toxicity and/or complications of previous anti-cancer treatments such as chemotherapy, surgery, and radiotherapy, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for alopecia and irrecoverable permanent radiation damage. 7. A tendency to coagulopathy or bleeding, including an arterial or venous thromboembolic event (including a history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism) within 6 months before randomization; Any life-threatening bleeding event (including the need for blood transfusion, surgical or local treatment, or continued medical therapy) or major vascular invasion was considered by the investigator to be bleeding prone. 8. With severe cardiac diseases, such as any severe cardiac arrhythmias (including ventricular arrhythmias, supraventricular and other arrhythmias uncontrolled by medications), cardiac dysfunction of grade III or higher (New York Heart Association [NYHA], see Appendix 4 for details), and echocardiography showing left ventricular ejection fra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the incidence, type, severity, duration, outcome, and correlation with study drugs of AEs, SAEs, abnormal laboratory test values, physical examination and vital sign abnormalities.;Plasma concentrations of PLB1004 and metabolites;Refer to RECIST v1.1, ORR?DoR?DCR assessed by Blind Independent Center Review Committee (BICR) and the investigator;Overall Survival;Refer to RECIST v1.1, PFS assessed by the investigator; | — |
Countries
China
Contacts
Public ContactWu Yilong, Chongrui Xu
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed