Clinical trial NCT04351555: A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer
Official title: A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-04-17
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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
* 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 \[IASLC Staging Manual in Thoracic Oncology 2016\]).
* Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised 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 (eg., 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 (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.
* Patients who have pre-operative radiotherapy treatment as part of their care plan
* Mixed small cell and NSCLC histology
* Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC
* 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.
* 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)

Primary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: From date of randomization to an average of 12 weeks after the first dose
Secondary outcomes:
measure: Pathological complete response (pCR)
timeFrame: From date of randomization to an average of 12 weeks after the first dose
measure: Event-free survival (EFS)
timeFrame: From date of randomization up to approximately 5.5 years after the last patient is randomized
measure: Overall Survival (OS)
timeFrame: From date of randomization up to approximately 5.5 years after the last patient is randomized
measure: Disease free survival (DFS)
timeFrame: From date of randomization up to approximately 5.5 years after the last patient is randomized
measure: Downstaging
timeFrame: From date of randomization to an average of 12 weeks after the first dose
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)
timeFrame: From date of randomization up to approximately 5.5 years after the last patient is randomized
measure: Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA
timeFrame: Baseline
measure: Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples
timeFrame: Baseline
measure: PK plasma concentrations of osimertinib
timeFrame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
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)
timeFrame: From date of randomization up to approximately 5.5 years after the last patient is randomized
Other outcomes:
measure: Cure rate
timeFrame: From the surgery until 5 years after surgery
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
timeFrame: 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-surgery
measure: MPR using plasma-derived circulating-free tumour DNA (ctDNA)
timeFrame: From date of randomization to an average of 12 weeks after the first dose
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Irvine
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Commack
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Graz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Jau
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Recife
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Santa Maria
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Panagyurishte
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Las Condes
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nantong
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wanzhou
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Avignon Cedex
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research Site
city: Esslingen a.N.
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Namakkal
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Varanasi
country: India
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Akashi-shi
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Hwasun-gun
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Yangsan-si
country: Korea, Republic of
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: D.F
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: La Libertad
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Winterthur
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Pathumthani
country: Thailand
facility: Research Site
city: Phisanulok
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Memorial Sloan Kettering, USA
name: Jamie Chaft, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Center Hospital East, Japan
name: Masahiro Tsuboi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thoraxchirurgie Bethanien, Switzerland
name: Walter Weder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021 Nov;17(31):4045-4055. doi: 10.2217/fon-2021-0549. Epub 2021 Jul 19.