This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer
Name: Osimertinib
Name: Cisplatin
Name: Carboplatin
Name: Placebo
Name: Pemetrexed
Description: Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery
Measure: Major Pathological Response (MPR) Time: From date of randomization to an average of 12 weeks after the first doseDescription: Defined as absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery
Measure: Pathological complete response (pCR) Time: From date of randomization to an average of 12 weeks after the first doseDescription: An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause
Measure: Event-free survival (EFS) Time: Up to approximately 42 months after the last patient is randomizedDescription: Patients will be followed up to approximately 5.5 years after they are randomized.
Measure: Overall Survival (OS) Time: Up to approximately 5.5 years after the last patient is randomizedDescription: DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.
Measure: Disease free survival (DFS) Time: From date of randomization up to approximately 42 months after date of resectionDescription: Measured using pathologic mediastinal lymph node evaluation
Measure: Downstaging Time: From date of randomization to an average of 12 weeks after the first doseDescription: Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
Measure: Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items) Time: From randomization to 264 weeks post-surgeryDescription: Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy
Measure: Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items) Time: From randomization to 264 weeks post-surgeryDescription: The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here 5-year landmark cure rate will be calculated in the same time as OS analysis.
Measure: Cure rate Time: From the surgery until 5 years after surgeryDescription: Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment
Measure: Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone Time: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgeryAllocation: Randomized
Parallel Assignment
There are 3 SNPs
- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R ---
- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R --- --- T790M --- --- L861Q ---
- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R --- --- T790M ---