Neoadjuvant Osimertinib + Chemotherapy for EGFR-mutant Stage III NSCLC

Study Overview
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Brief Summary
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This is a phase II, single-arm, multi-center study of neoadjuvant osimertinib in combination with chemotherapy for the treatment of patients with resectable EGFR-mutant stage III (N2) non-squamous non-small cell lung cancer

Official Title
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Neoadjuvant Osimertinib Plus Chemotherapy for EGFR-mutant Stage III N2 Non-squamous Non-small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Osimertinib
* Drug: Cisplatin
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented N2 positive non-squamous NSCLC with resectable (Stage IIIA or T3-4N2 IIIB) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]). Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialized in oncologic procedures). 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). Exclusion Criteria: Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. History of another primary malignancy, except for the following: Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of investigational product (IP) and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease; Adequately treated carcinoma in situ without evidence of disease Patients who have pre-operative radiotherapy treatment as part of their care plan Mixed small cell and NSCLC histology T4 tumours infiltrating the aorta, the oesophagus and/or the heart; and/or any bulky N2 disease deemed unresectable Patients who are candidates to undergo only segmentectomies or wedge resections Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug Prior treatment with EGFR-TKI therapy 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: osimertinib plus chemotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: osimertinib plus chemotherapy<br>Osimertinib (80mg/qd) po. for 60 days with two cycles of Pemetrexed (500 mg/m2) to be administered with cisplatin (75mg/m2) on Day 1 of every 3-week cycle for 2 cycles | Drug: Osimertinib<br>* 80mg/qd oral for 60 days<br>* Other names: TAGRISSO;Drug: Cisplatin<br>* Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 2 cycles.<br>* Other names: DDP;Drug: Pemetrexed<br>* Pemetrexed (500 mg/m2) to be administered with cisplatin on Day 1 of every 3-week cycle for 2 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete lymph node clearance rate | the ratio of ypN0 percentage after resection | From date of enrollment to an average of 12 weeks after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) | Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery | From date of enrollment to an average of 12 weeks after the first dose | 
| Pathological complete response (pCR) | Defined as absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery | From date of enrollment to an average of 12 weeks after the first dose | 
| Downstaging | Measured using pathologic mediastinal lymph node evaluation | From date of enrollment to an average of 12 weeks after the first dose | 
| 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. | From date of enrollment up to approximately 42 months after date of resection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non small cell lung cancer, neoadjuvant, EGFR-TKI