This study is designed as a multi-cohort trial based on various patient biomarkers study with the potential to include new study treatment in the future. EGFR-sensitive mutation-positive patients with distant recurrence after adjuvant osimertinib treatment for EGFRm resectable SIB-IIIA NSCLC and scheduled to receive osimertinib plus chemotherapy will be enrolled in cohort 1. In this cohort, approximately 100 patients will be recruited from 25 sites in China. The enrolment period is planned to be approximately 16 months.

Inclusion Criteria for pre-screening:

1. Prior complete surgical resection (R0) and adjuvant osimertinib in EGFRm resectable SIB-IIIA NSCLC (AJCC 7th edition).
2. Off-treatment recurrence (including completed 3 years adjuvant osimertinib & discontinued adjuvant osimertinib before 3 years due to non-recurrence reason).
3. Newly diagnosed distant recurrent NSCLC (IVA or IVB) (per Version 9 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
4. ≥6 months interval between recurrence and completion or discontinuation of adjuvant osimertinib.
5. Histologically/cytologically confirmed nonsquamous NSCLC (Investigators confirmed recurrence of primary lesion allowed if biopsy not available)
6. No prior systemic anti-cancer therapy after adjuvant therapy, but can receive local therapy (including surgery, radiotherapy, etc. per investigator choice).
7. Patients with asymptomatic or stable CNS metastases allowed.

Inclusion Criteria for screening:

1. Male or female, at least 18 years of age. Type of patient and disease characteristics
2. EGFR mutation (Exon 19del/Exon 21 L858R)-reconfirmed for study entry (mandatory undergo NGS by plasma, and tissue if applicable).
3. Life expectancy >12 weeks at Day 1.

Exclusion Criteria:

1. Patients with only local/regional recurrence.
2. Spinal cord compression and symptomatic brain metastases.
3. Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
4. Adjuvant osimertinib therapy was discontinued due to the occurrence of severe adverse events.
5. Prior with other adjuvant EGFR-TKIs (excluding osimertinib).
6. 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.
7. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
8. Contraindication for pemetrexed and cisplatin/carboplatin according to local approved label.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.