Osimertinib Plus Chemotherapy vs Osimertinib in EGFRm NSCLC With Persistence Week-3 ctDNA EGFRm After 1L Osimertinib

Inclusion Criteria: * Provision and signed of informed consent prior to any study specific procedures; * Male or female, aged at least 18 years; * Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1; * Newly diagnosed, and histologically documented metastatic non-squamous NSCLC with sensitizing EGFR mutations positive, and classified as stage IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy; * Life expectancy of at least 3 months at recruitment; * Only the patients receiving osimertinib as 1L treatment and meeting the following criteria will be considered: A. Prior to 1L osimertinib: 1. History of EGFRm (exon 19 deletion or exon 21 L858R) in the plasma ctDNA by the local testing methods. 2. No previous systemic treatment. Adjuvant therapies, or definitive radiation/chemoradiation are permitted as long as treatment was completed at least 6 months prior to receiving 1L treatment. 3. Patients with asymptomatic and stable CNS metastases for at least 2 weeks will be allowed, including leptomeningeal metastases. B. Prior to randomization: Patients after 3 weeks of 1L osimertinib treatment who have persistence ctDNA EGFRm by SuperARMS at 3 weeks will be considered to be enrolled. They will need to further meet the criteria below before randomization: 1. Patients without disease progression by RECIST 1.1 evaluation; 2. At least 1 measurable extracranial lesion according to RECIST 1.1 . 3. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. 4. Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. Exclusion Criteria: * Involvement in the planning and/or conduct of the study; * History of hypersensitivity to active or inactive excipients of Osimertinib and/or Pemetrexed and/or Carboplatin or drugs with a similar chemical structure or class to Osimertinib and/or Pemetrexed and/or Carboplatin; * For patients, inability to collect plasma samples at baseline and disease progression; * QT prolongation or any clinically important abnormalities in rhythm; * Any evidence of severe or uncontrolled systemic diseases; * Currently receiving medications or herbal supplements known to be strong inducers of CYP3A4; * Any unresolved toxicities from prior therapy greater than CTCAE 5.0 grade 1 at the time of starting study treatment. * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib. * Inadequate bone marrow reserve or organ function; * Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. * Contraindication for osimertinib, pemetrexed and carboplatin according to China approved label. * Women who are pregnant or breast-feeding.