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 locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology ), and classified as stage IIIB, IIIC, 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.
