Uncommon EGFRm NSCLC
Conditions
Interventions
Intervention group:Osimertinib with Platinum plus Pemetrexed Chemotherapy
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Provision of signed and dated, written informed consent form prior to any mandatory studyspecific procedures, sampling, and analyses. 3. Male or female, >= 18 years old. 4. Pathologically confirmed nonsquamous NSCLC. 5. Newly diagnosed with locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB), or recurrent NSCLC (according to the International Association for the Study of Lung Cancer [IASLC] Thoracic Tumor Staging Manual [8th Edition])]), and are not suitable for radical surgery or radiotherapy. 6. According to the ARMS or Super-ARMS or NGS test results of tumor tissue or plasma from a certified laboratory approved by Chinese regulatory authorities, the tumor carries at least one of the 4 rare EGFR mutations (G719X/L861Q/S768I/T790M) (single mutation or compound mutation), but not other EGFR mutations (including ex19del/L858R). 7. Subjects must be eligible (as assessed by the investigator) and will be receiving standard treatment (pemetrexed + carboplatin or cisplatin for 4-6 cycles followed by pemetrexed maintenance therapy). 8. The subjects must be untreated advanced NSCLC patients who are not suitable for radical surgery or radiotherapy. For previously received adjuvant and neoadjuvant therapy (chemotherapy, radiotherapy, immunotherapy, biological therapy, experimental drugs) or radical radiotherapy/chemoradiotherapy with or without combination therapy including immunotherapy, biological therapy, experimental drugs. Patients who had completed the aforementioned treatment at least 6 months before the onset of recurrent disease were allowed to enroll. 9. Subjects with stable CNS metastases can be enrolled in the study. 10. ECOG/WHO PS score of 0 to 1 at screening and no clinically significant worsening within the past 2 weeks. 11. Subject's life expectancy > 12 weeks on study day 1. 12. At least one lesion at baseline that can be accurately measured by CT or MRI (longest diameter >= 10 mm; except for lymph nodes, whose short axis must be >= 15 mm) and suitable for accurate repeat measurement, has not previously received radiotherapy. If only 1 measurable lesion was present, it could be used (as a target lesion) as long as the lesion had not been previously irradiated and had not been biopsied within 14 days prior to the baseline tumor assessment scan. 13. Female patients must be on highly effective contraceptive measures, must not be breastfeeding, and must have a negative pregnancy test prior to the first dose of the study intervention, or must meet one of the following criteria at screening to demonstrate their infertility ability: (1) Postmenopausal (defined as age > 50 years and amenorrhea for at least 12 months after discontinuation of all exogenous hormone therapy); (2) Women under the age of 50 who have amenorrhea for >= 12 months after stopping exogenous hormone therapy and whose luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels have dropped to the postmenopausal range specified by the research institution will also be considered postmenopausal women ; (3) Documented records of irreversible sterilization procedures such as hysterectomy, bilateral oophorectomy or bilateral salpingectomy (except tubal ligation). 14. Male subjects must use barrier contraception.
Exclusion criteria
Exclusion criteria: 1. Spinal cord compression, symptomatic and unstable brain metastases, excluding subjects who have completed curative treatment, steroid-negative, and neurologically stable subjects for at least 2 weeks after completing curative treatment and steroid treatment. Subjects with asymptomatic brain metastases may be enrolled in the study, provided the investigators believe that immediate curative treatment is not required. 2. History of previous ILD, drug-induced ILD, radiation pneumonitis requiring steroid therapy, or evidence of clinically active ILD. 3. There is any evidence of severe and uncontrolled systemic disease, including uncontrolled hypertension and active bleeding tendency (the investigator believes that these subjects should not participate in the trial or that these diseases may affect protocol compliance), or active infection, including any patient being treated for an infection, not limited to hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Chronic disease screening is not required. 4. Meet any of the following cardiac criteria: (1) According to the QTcF value obtained by the clinical screening ECG machine and the results of 3 electrocardiogram (ECG) examinations, the average resting corrected QT interval (QTc) is > 470 ms; (2) Any clinically significant resting ECG rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third-degree heart block, and second-degree heart block; (3) The presence of any factors that increase the risk of QTc prolongation or arrhythmic events, such as electrolyte abnormalities (including: serum/plasma potassium, magnesium and calcium 2.5 x ULN in the absence of obvious liver metastases or > 5 x ULN in the presence of liver metastases; (5) AST > 2.5 x ULN in the absence of liver metastasis, or > 5 x ULN in the presence of liver metastasis; (6) Total bilirubin > 1.5 x ULN in the absence of liver metastases, or > 3 x ULN in the presence of Gilbert syndrome (high unconjugated bilirubinemia) or in the presence of liver metastases; (7) Calculate the creatinine clearance rate < 60 mL/min using the Cockcroft and Gault formula. 6. Any combined and/or other active malignancies requiring treatment within 2 years prior to the first dose of study intervention therapy (osimertinib). 7. With the exception of alopecia and grade 2 neuropathy associated with previous platinum-containing therapy, any unresolved CTCAE grade 1 or higher toxicity at the time of initiation of study intervention therapy (such as adjuvant chemotherapy). 8. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous major bowel resection that would prevent adequate absorption of osimertinib. 9. Previous use of any systemic anticancer thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR(Objective Response Rate); | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety;Tolerance; | — |
Countries
China
Contacts
Public ContactLu You
West China Hospital of Sichuan University
Outcome results
None listed