Combining Afatinib and Concurrent Chemotherapy, Followed by Osimertinib and Concurrent Chemotherapy, in Untreated EGFR Positive NSCLC Tumors

Inclusion Criteria:

1. Histologically confirmed NSCLC, positive for non-exon20insertion uncommon EGFR mutations that are eligible for afatinib therapy in first line
2. WHO PS 0-2
3. Be willing and able to provide written informed consent for the trial.
4. Be above 18 years of age on day of signing informed consent.
5. Patients must have radiological measurable disease
6. Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of metastatic NSCLC.

Exclusion Criteria:

1. Inability to provide informed consent
2. Inability to take study medications
3. Patients with symptomatic or unstable CNS metastases
4. Prior EGFR TKI or platinum-doublet therapy for advanced stage NSCLC. Prior (neo)adjuvant treatments are allowed when the last administration is one year or more.
5. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
6. Active infection requiring systemic therapy.
7. Active Hepatitis B or C.
8. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit.