Osimertinib Plus Chemotherapy in Uncommon EGFRm NSCLC

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 study-specific procedures, sampling, and analyses. 3. Male or female, at least 18 years of age. 4. Pathologically confirmed nonsquamous NSCLC. 5. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer \[IASLC\] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy. 6. The tumour harbors at least 1 of the 4 uncommon EGFR mutations (G719X/L861Q/S768I/T790M), either alone or in combination, which not include other EGFR mutations including ex19del /L858R, assessed by one of ARMS, Super-ARMS or NGS analysis on the basis of tumour tissue or plasma testing from accredited laboratories approved by the Chinese regulatory authority. 7. Participants must be considered suitable by investigator and about to receive standard of care which composed of pemetrexed plus carboplatin or cisplatin for 4 to 6 cycles followed by pemetrexed maintenance. 8. Participants must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 6 months prior to the development of recurrent disease. 9. Stable CNS metastases participants will be allowed. 10. ECOG/WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks. 11. Life expectancy \>12 weeks at Day 1. 12. At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumour assessment scans. 13. Female must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study intervention or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening: * Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments * Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. Further information is available in Appendix E (Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods). 14. Male participants must be willing to use barrier contraception. Exclusion Criteria: 1.Spinal cord compression; symptomatic and unstable brain metastases, except for those participants who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids. Participants with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated. 2 Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD. 3 Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol, or active infection including any patients receiving treatment for infection but not limited to hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 4.Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value; * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; eg, complete left bundle branch block, third-degree heart block, second-degree heart block; * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium\*, magnesium\* and calcium\* below the lower limit of normal (LLN), heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes. 5.Inadequate bone marrow or organ function reserve as demonstrated by any of the following laboratory values: * Absolute neutrophil count below the LLN \* * Platelet count below the LLN\* * Hemoglobin \<90 g/L\* \*The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted. * ALT \>2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or \>5 x ULN in the presence of liver metastases * AST \>2.5 x ULN if no demonstrable liver metastases or \>5 x ULN in the presence of liver metastases * Total bilirubin \>1.5 x ULN if no liver metastases or \>3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases * Creatinine clearance \<60 mL/min calculated by Cockcroft and Gault equation (refer to Appendix G for appropriate calculation) 6.Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study intervention (osimertinib, carboplatin and pemetrexed). 7 Any unresolved toxicities from prior therapy (eg, adjuvant chemotherapy) greater than CTCAE Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy. 8 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. 9.Prior treatment with any systemic anti-cancer therapy for advanced NSCLC not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including biologic therapies, investigational agents are permitted as long as treatment was completed at least 6 months prior to the development of recurrent disease. 10.Prior treatment with an EGFR-TKI or immune-oncology (IO) therapy. 11.Major surgery within 4 weeks of the first dose of study intervention. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery (VATS) are permitted. 12.Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study intervention. 13.Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior) (Appendix F). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. 14.Participation in another clinical study with an investigational product during the 4 weeks prior to Day 1. Participants in the follow-up period of an interventional study are permitted. 15.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at the study site). 16.Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements. 17.Previously enrolled in the present study. 18.Currently pregnant (confirmed with positive pregnancy test) or breast-feeding. 19.History of hypersensitivity to active or inactive excipients of study intervention or drugs with a similar chemical structure or class to study intervention. 20.In addition, the following conditions are considered criteria for exclusion: * Prior allogeneic bone marrow transplant * Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.