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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
358
Oral
Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
Major Pathological Response (MPR)
Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery
Time frame: From date of randomization to an average of 12 weeks after the first dose
Pathological complete response (pCR)
Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery
Time frame: From date of randomization to an average of 12 weeks after the first dose
Event-free survival (EFS)
An event is defined as documented disease progression that precludes surgery or prevents completion of definitive surgery; recurrence or a new lesion, local or distant (a new primary malignancy, confirmed by pathology if clinically feasible, is not considered to be an EFS event); death due to any cause
Time frame: From date of randomization up to approximately 5.5 years after the last patient is randomized
Overall Survival (OS)
OS will be defined as the time from the date of randomisation until death due to any cause
Time frame: From date of randomization up to approximately 5.5 years after the last patient is randomized
Disease free survival (DFS)
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.
Time frame: From date of randomization up to approximately 5.5 years after the last patient is randomized
Downstaging
Measured using pathologic mediastinal lymph node evaluation
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Oral
Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Research Site
Duarte, California, United States
Research Site
Irvine, California, United States
Research Site
San Francisco, California, United States
Research Site
Santa Monica, California, United States
Research Site
Santa Rosa, California, United States
Research Site
Boston, Massachusetts, United States
Research Site
Lebanon, New Hampshire, United States
Research Site
Commack, New York, United States
Research Site
New York, New York, United States
Research Site
Houston, Texas, United States
...and 148 more locations
Time frame: From date of randomization to an average of 12 weeks after the first dose
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)
Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients
Time frame: From date of randomization up to approximately 5.5 years after the last patient is randomized
Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA
Time frame: Baseline
Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples
Time frame: Baseline
PK plasma concentrations of osimertinib
Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
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)
Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy
Time frame: From date of randomization up to approximately 5.5 years after the last patient is randomized