A Randomized Phase II Study of LAZE Rti N ib Alone Versus Lazertinib Plus Beva C Izumab for A Dvanced Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor Activating Mutations and Smoking History
Using gefitinib or Osimertinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with active mutations in epithelial cell growth factor receptors (EGFR), 70% response rate (CR+PR) and 90% disease control rate (CR+PR+SD) compared to the current non-small cell therapy, which is significant in the EFRT treatment. However, resistance causes recurrence in most patients. Therefore, it is necessary to develop a more effective treatment. Recently, in Japan, combined allotinib and bevacizumab therapy as primary therapy in non-small cell lung cancer patients with EGFR mutation improved PFS statistically significantly compared to allotinib monotherapy, suggesting the possibility of a new treatment (Hazard ratio 0.605, 95% CI 0.417-0.877, P=0.016). In addition, subsequent osmutinib and bevacizumab combination therapy showed a significant difference in PFS in the smoker group, although they did not show significant improvement in PFS in the entire patient group. (Hazard ratio 0.605, 95% CI 0.417-0.877, P=0.016). Since EGFR mutated lung cancer is highly frequent in Korea, it is necessary to develop more effective treatments for such patients. Therefore, we propose this clinical trial to find out the efficacy of lasertinib and bevacizumab combination therapy.
• Histologically confirmed patients with locally progressive or metastatic non-small cell lung cancer (IIIB or IV) who have not been diagnosed as squamous cell carcinoma.
• Patients with one or more measurable lesions in accordance with the RECIST criteria (Version 1.1), tumor lesions located at the previous irradiation site, are considered measurable if progress has been made in those lesions.
• Patients with institutionalized EGFR mutation (exon 19 deletion or L858R)
• Patients with a history of smoking, including those who are currently smoking (defined as those who have smoked more than 100 cigarettes in their lifetime)
• ECOG PS 0-1 Patient
• Patients with appropriate hematological functions ANC≥1,500/uL, hemoglobin≥9.0g/dL, platelet≥100,000/uL
• Patients with adequate liver function Total bilirubin \< 1 x UNL, AST (SGOT) and ALT (SGPT) \< 2.5 x UNL (If there is an interruption: total bilirubin \<3 x UNL, AST (SGOT) and ALT (SGPT) \<5 x UNL)
• a patient with appropriate renal function Cr UN UNL, however, can be registered if the creatinine clearance calculated according to the formula Cocroft and Gault is 50 50 ml/min outside the normal range.
• Proteinuria test \<2+ (if 22+ then protein 11g must be in 24-hour urine test)
• Patients with a history of receiving radiation therapy must meet the following criteria.
• \- In the case of direct radiation irradiation to the lung lesion area, it must have elapsed at least 12 weeks from the time of registration.
⁃ In the case of chronic radiation therapy for intracoracic bone metastasis, it must be at least 12 weeks from the time of registration.
⁃ 2 weeks or more from the time of registration if radiotherapy has been performed on any non-chest area Must be elapsed.
⁃ At the time of registration, the date of completion of the previous treatment or procedure must pass the period specified below.
⁃ \- Surgery (including exploratory/experimental thoracotomy): 4 weeks
⁃ \- Pericardial drainage: 1 week
⁃ \- pleural adhesion not attributed to anti-species positive substances (including biological response regulators such as Picibanil): 2 weeks
⁃ \- Tissue biopsy to confirm selection criteria (including biopsy using thoracoscope): 1 week
‣ Procedures for the treatment of trauma (unregistered patients with untreated wounds): 2 weeks
‣ Blood transfusion, hematopoietic growth factor administration: 2 weeks
‣ The puncture and aspiration cell test: 1 week
‣ Administration of other clinical trial medications: 4 weeks
⁃ Women in childbearing age should be negative in serum or urine pregnancy tests within 7 days prior to test treatment.
⁃ Male and childbearing female test subjects with female partners' pregnancy must agree to use the following two high-efficiency test methods for at least 180 days after the last dose of the assigned treatment is administered. Bevacizumab can also damage a woman's reproductive ability. Therefore, women who have entered the bevacizumab combination group should be preceded by discussions on preserving the reproductive ability of women who are likely to become pregnant before treatment - asceticism
⁃ \- tubal ligation
⁃ \- Hormone contraceptives that do not cause drug interactions (such as Mirena)
‣ Medroxyprogesterone injection (Depo-Provera)
‣ Copper bands and intrauterine devices
‣ a partner's vasectomy
‣ Partner's use of condoms
⁃ Patients who have agreed to the clinical trial-