Clinical trial • Phase III • Oncology
OSIMERTINIB for Non-small cell lung cancer (non-squamous, resectable Stage II–IIIB N2) | EGFR mutation-positive resectable non-small cell lung cancer
Phase III trial of OSIMERTINIB for Non-small cell lung cancer (non-squamous, resectable Stage II–IIIB N2) | EGFR mutation-positive resectable non-small ce…
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Non-small cell lung cancer (non-squamous, resectable Stage II–IIIB N2) | EGFR mutation-positive resectable non-small cell lung cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 27-03-2024
- First CTIS Authorization Date
- 14-05-2024
Trial design
Randomised, three-arm randomised design: osimertinib monotherapy arm; osimertinib in combination with chemotherapy arm; standard-of-care chemotherapy alone arm (chemotherapy agents used in the study include pemetrexed, cisplatin and carboplatin as listed in the product information). doses and full schedules are not specified in the ctis json.-controlled Phase III trial in Spain, Poland, France and others.
- Randomised
- Yes
- Comparator
- Three-arm randomised design: osimertinib monotherapy arm; osimertinib in combination with chemotherapy arm; standard-of-care chemotherapy alone arm (chemotherapy agents used in the study include pemetrexed, cisplatin and carboplatin as listed in the product information). Doses and full schedules are not specified in the CTIS JSON.
- Target Sample Size
- 295
Eligibility
Recruits 295 isVulnerablePopulationSelected = true; For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. Subject information and informed consent forms are provided in multiple country/language versions (examples in Spanish, Polish, French, German, Italian, Bulgarian and other local language ICFs)..
- Vulnerable Population
- isVulnerablePopulationSelected = true; For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. Subject information and informed consent forms are provided in multiple country/language versions (examples in Spanish, Polish, French, German, Italian, Bulgarian and other local language ICFs).
Inclusion criteria
- {"criterion_text":"- Male or female, at least 18 years of age. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.\n- Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]).\n- Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a Mulit-disciplinary Team (MDT) evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).\n- 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.\n- 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
- {"criterion_text":"- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.\n- 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)\n- History of another primary malignancy (including any known or suspected synchronous primary lung cancer), 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; Any synchronous Stage IA primary lung cancer that is ≤2 cm and planned to be resected during surgery for the Stage II to IIIB N2 lung tumour.\n- Patients who have pre-operative radiotherapy treatment as part of their care plan\n- Mixed small cell and NSCLC histology\n- Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC\n- T4 tumours infiltrating the great vessels, the carina, the trachea, the oesophagus, the heart, and/or the vertebral body; and/or any bulky N2 disease.\n- Patients who are candidates to undergo only segmentectomies or wedge resections\n- Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug\n- Prior treatment with EGFR-TKI therapy"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Major Pathological Response (MPR) (≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post surgery)","definition_or_measurement_approach":"MPR defined as ≤10% residual cancer cells in the main tumour, assessed by the central pathology laboratory post surgery"}
Secondary endpoints
- {"endpoint_text":"- Complete pathological Response (pCR) (absence of any residual cancer cells in the dissected tumour samples, including the main tumour and lymph nodes, assessed post-surgery); EFS; DFS; Downstaging; Overall Survival (OS)","definition_or_measurement_approach":"pCR defined as absence of any residual cancer cells in dissected tumour samples, including main tumour and lymph nodes, assessed post-surgery; EFS, DFS, Downstaging and OS assessed as specified in protocol (no further detail in CTIS record)"}
- {"endpoint_text":"- Change from baseline in Patient reported outcomes (ePRO)","definition_or_measurement_approach":"Change from baseline in patient-reported outcomes measured by ePRO instruments (as specified in protocol)"}
- {"endpoint_text":"- Concordance of EGFRm status between tumour tissue DNA and patientmatched plasma-derived ctDNA","definition_or_measurement_approach":"Concordance assessment comparing EGFR mutation status in baseline tumour tissue DNA and matched plasma-derived ctDNA"}
- {"endpoint_text":"- Concordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples.","definition_or_measurement_approach":"Concordance assessment between local cobas® EGFR Mutation Test v2/ FoundationOne CDx results used for selection and retrospective central cobas® EGFR Mutation Test v2 results on baseline tumour samples"}
- {"endpoint_text":"- PK plasma concentrations of osimertinib","definition_or_measurement_approach":"Pharmacokinetic plasma concentration measurements of osimertinib"}
Recruitment
- Planned Sample Size
- 295
- Recruitment Window Months
- 69
- Consent Approach
- Informed consent obtained using subject information sheets and ICFs. Adult participants provide written informed consent. For patients aged <20 years enrolled in Japan, written informed consent should be obtained from the patient and his or her legally acceptable representative. ICFs and related materials are available in multiple local language versions (examples in the document list: Spanish, Polish, French, German, Italian, Bulgarian, and country-specific ICFs).
Geography
- Total Number Of Sites
- 19
- Total Number Of Participants
- 40
Spain
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 09-07-2025
- Processing Time Days
- 443
- Number Of Sites
- 5
- Number Of Participants
- 7
Sites
- Site Name
- Hospital Universitario Puerta De Hierro De Majadahonda
- Department Name
- Oncologia
- Contact Person Name
- Mariano Provencio Pulla
- Contact Person Email
- mprovencio.ensayosclinicos@gmail.com
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Oncologia
- Contact Person Name
- Manuel Domine Gomez
- Contact Person Email
- manueldomine@gmail.com
- Site Name
- Hospital Universitario Regional De Malaga
- Department Name
- Oncologia
- Contact Person Name
- Manuel Cobo Dols
- Contact Person Email
- manuelcobodols@yahoo.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncologia
- Contact Person Name
- Alex Marinez Marti
- Contact Person Email
- alex.martinez@vhebron.net
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Oncologia
- Contact Person Name
- Jose Luis Gonzalez Larriba
- Contact Person Email
- jglarriba@salud.madrid.org
Poland
- Earliest CTIS Part Ii Submission Date
- 13-05-2024
- Latest Decision Or Authorization Date
- 09-07-2025
- Processing Time Days
- 422
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Warminsko-Mazurskie Centrum Chorob Pluc W Olsztynie
- Department Name
- Oddział Onkologii z Pododdziałem chemioterapii
- Contact Person Name
- Jaroslaw Kolb-Sielecki
- Contact Person Email
- j.kolbsielecki@gmail.com
France
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 08-07-2025
- Processing Time Days
- 442
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Polyclinique Bordeaux Nord Aquitaine
- Department Name
- Hemato Onco-radiothérapie
- Contact Person Name
- Sigolène Galland-Girodet
- Contact Person Email
- m.leblay@gbna-sante.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 07-07-2025
- Processing Time Days
- 441
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Martha-Maria Krankenhaus Halle-Doelau gGmbH
- Department Name
- Studiensekretariat MVZ
- Contact Person Name
- Wolfgang Schütte
- Contact Person Email
- wolfgang.schuette@martha-maria.de
- Site Name
- Pius-Hospital Oldenburg
- Department Name
- Klinik für Hämatologie und Onkologie
- Contact Person Name
- Frank Griesinger
- Contact Person Email
- Frank.Griesinger@Pius-Hospital.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Klinik für Innere Medizin I, Sektion Klinische Forschung & ECTU
- Contact Person Name
- Justyna Rawluk
- Contact Person Email
- justyna.rawluk@uniklinik-freiburg.de
Italy
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 08-07-2025
- Processing Time Days
- 442
- Number Of Sites
- 4
- Number Of Participants
- 6
Sites
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- Oncologia Polmonare
- Contact Person Name
- Silvia Novello
- Contact Person Email
- silvia.novello@unito.it
- Site Name
- Humanitas Research Hospital
- Department Name
- Oncologia
- Contact Person Name
- Giovanna Finocchiaro
- Contact Person Email
- giovanna.finocchiaro@cancercenter.humanitas
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- Oncologia Medica
- Contact Person Name
- Diego Cortinovis
- Contact Person Email
- diegoluigi.cortinovis@irccs-sangerardo.it
- Site Name
- Istituto Tumori Bari Giovanni Paolo II
- Department Name
- Oncologia Medica Toracica
- Contact Person Name
- Domenico Galetta
- Contact Person Email
- galetta@oncologico.bari.it
Austria
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 23-07-2025
- Processing Time Days
- 457
- Number Of Sites
- 2
- Number Of Participants
- 16
Sites
- Site Name
- Krankenhaus Nord Klinik Floridsdorf
- Department Name
- Department for internal medicine and pneumology
- Contact Person Name
- Maximilian Hochmair
- Contact Person Email
- maximilian.hochmair@gesundheitsverbund.at
- Site Name
- Universitätsklinikum Graz
- Department Name
- Department for oncology
- Contact Person Name
- Gudrun Absenger
- Contact Person Email
- gudrun.absenger@medunigraz.at
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 22-04-2024
- Latest Decision Or Authorization Date
- 23-07-2025
- Processing Time Days
- 457
- Number Of Sites
- 3
- Number Of Participants
- 3
Sites
- Site Name
- UMHAT Sofiamed OOD
- Department Name
- Department of Medical Oncology
- Contact Person Name
- Velko Minchev
- Contact Person Email
- v_minchev@abv.bg
- Site Name
- Multi-profile Hospital for Active Treatment Heart and Brain EAD
- Department Name
- Medical Oncology Clinic
- Contact Person Name
- Nataliya Chilingirova
- Contact Person Email
- n.chilingirova.pn@heartandbrain.bg
- Site Name
- Multiprofile Hospital For Active Treatment-Uni Hospital Ltd.
- Department Name
- Department of Medical Oncology
- Contact Person Name
- Rossitza Krasteva
- Contact Person Email
- rkr_2002@yahoo.com
Sponsor
Primary sponsor
- Full Name
- AstraZeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- TAGRISSO 40 mg film-coated tablets
- Active Substance
- OSIMERTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU/1/16/1086/003
- Maximum Dose
- 40 mg
- Investigational Product Name
- TAGRISSO 80 mg film-coated tablets
- Active Substance
- OSIMERTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Authorisation Status
- EU/1/16/1086/004
- Maximum Dose
- 40 mg
- Investigational Product Name
- Armisarte 25 mg/ml concentrate for solution for infusion
- Active Substance
- PEMETREXED
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Authorisation Status
- EU/1/15/1063/002
- Maximum Dose
- 500 mg/m2
- Investigational Product Name
- CISPLATIN
- Active Substance
- CISPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Maximum Dose
- 75 mg/m2
- Investigational Product Name
- CARBOPLATIN
- Active Substance
- CARBOPLATIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- INTRAVENOUS
- Maximum Dose
- 2250 mg/m2
- Investigational Product Name
- PLACEBO
- Active Substance
- PLACEBO
- Modality
- Other
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 40 mg
- Combination Treatment
- Yes
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