OSIMERTINIB for Non-small cell lung cancer (Stage III) | EGFR mutation-positive non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Male or female aged at least 18 years"}
• {"criterion_text":"- Patients with histologically documented NSCLC of predominantly nonsquamous Pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology)"}
• {"criterion_text":"- The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing (cobas® v2 only)"}
• {"criterion_text":"- Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy)"}
• {"criterion_text":"- Chemoradiation must be completed ≤6 weeks prior to randomization"}
• {"criterion_text":"- Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy"}
• {"criterion_text":"- World Health Organization (WHO) performance status of 0 or 1"}
• {"criterion_text":"- Life expectancy >12 weeks at Day 1"}
• {"criterion_text":"- Female patients who are not abstinent (in line with the preferred and usual lifestyle choice) must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-childbearing potential"}

Exclusion criteria

• {"criterion_text":"- Mixed small cell and non-small cell lung cancer histology"}
• {"criterion_text":"- Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease)"}
• {"criterion_text":"- Prior treatment with EGFR-TKI therapy"}
• {"criterion_text":"- Major surgery as defined by the investigator within 4 weeks of the first dose of study drug"}
• {"criterion_text":"- Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug)"}
• {"criterion_text":"- Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies"}
• {"criterion_text":"- History of interstitial lung disease (ILD) prior to chemoradiation"}
• {"criterion_text":"- Symptomatic pneumonitis following chemoradiation"}
• {"criterion_text":"- Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > Grade 2 from the prior chemoradiation therapy"}
• {"criterion_text":"- Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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"}
• {"criterion_text":"- Inadequate bone marrow reserve or organ function"}
• {"criterion_text":"- History of other malignancies, except: adequately treated nonmelanoma skin cancer or lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy"}
• {"criterion_text":"- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- PFS using BICR assessment according to RECIST v1.1 Sensitivity analysis of PFS using Investigator assessment according to RECIST v1.1","definition_or_measurement_approach":"Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1; sensitivity analysis using Investigator assessment per RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"- PFS in patients with EGFR Ex19del or L858R mutation and Patients with EGFRm+ Ex19del or L858R detectable in plasma-derived ctDNA using BICR assessment according to RECIST v1.1; Sensitivity analysis of PFS using Investigator assessment according to RECIST v1.1","definition_or_measurement_approach":"PFS by BICR per RECIST v1.1 in specified biomarker subgroups; sensitivity analysis by Investigator assessment"}
• {"endpoint_text":"- Time to CNS PFS (time to the earliest of CNS progression or death) using BICR assessments according to RECIST v1.1; Cumulative incidence rate of CNS PFS by BICR at 12 and 24 months","definition_or_measurement_approach":"Time to CNS progression or death by BICR per RECIST v1.1; cumulative incidence at 12 and 24 months"}
• {"endpoint_text":"- OS, ORR, DoR, DCR and tumor shrinkage, TTDM using BICR assessments according to RECIST v1.1, Time to treatment discontinuation (TTD)","definition_or_measurement_approach":"Overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), tumor shrinkage, and time to death or distant metastases (TTDM) assessed by BICR per RECIST v1.1; TTD as time to treatment discontinuation"}
• {"endpoint_text":"- Second progression free survival on a subsequent treatment (PFS2), Time to first subsequent therapy (TFST), Time to second subsequent therapy (TSST)","definition_or_measurement_approach":"PFS2 and time to subsequent therapies measured from progression as specified"}
• {"endpoint_text":"- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC QLQ-C30): Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Lung Cancer 13 items (EORTC QLQ-LC13)","definition_or_measurement_approach":"Change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores"}
• {"endpoint_text":"- Adverse Events (graded by CTCAE v5); Clinical chemistry, hematology and urinalysis; Vital signs (pulse and blood pressure), physical examination, weight; ECG parameters; Left ventricular ejection fraction; WHO Performance Status","definition_or_measurement_approach":"Safety assessments including AEs graded per CTCAE v5, laboratory tests, vitals, ECGs, LVEF, and WHO performance status"}
• {"endpoint_text":"- Trough plasma concentrations of osimertinib, and its metabolite AZ5104 If conducted, PK Parameters (CLss/F, Css, min and Css, max, AUCss) may be derived using population PK analysis and reported separately to the CSR. Data from this study may form part of a pooled analysis with data from other studies","definition_or_measurement_approach":"Pharmacokinetic assessment: trough concentrations and, if conducted, population PK-derived parameters (CLss/F, Css,min/max, AUCss)"}

Spain

Earliest CTIS Part Ii Submission Date

28-05-2024

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

514

Number Of Sites

5

Number Of Participants

10

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden