Clinical trial NCT05526755: A Study of 5 Years of Adjuvant Osimertinib in Completely Resected Epidermal Growth Factor Receptor Mutation (EGFRm) Non-small Cell Lung Carcinoma (NSCLC)
Official title: An Open-label, Single-arm, Phase II, Multinational, Multicentre Study to Assess the Efficacy and Safety of 5 Years of Osimertinib in Participants With EGFRm-positive Stage II-IIIB NSCLC, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stage II-IIIB Non-small Cell Lung Carcinoma
Keywords: Stage II-IIIB Non-small Cell Lung Cancer
Adjuvant osimertinib
Adjuvant chemotherapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-09-02
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of osimertinib in participants with EGFRm positive stage II-IIIB NSCLC, following complete tumour resection with or without adjuvant chemotherapy.

Detailed description: This is a phase 2 open-label study to assess the efficacy and safety of osimertinib in participants with stage II-IIIB NSCLC with sensitising EGFR mutations. The study is designed to evaluate 5 years of adjuvant osimertinib therapy.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged at least 18 years.
2. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
3. Magnetic Resonance Imaging (MRI) or contrast computed tomography (CT) scan of the brain.
4. Participants must be classified post-operatively as Stage II, IIIA, or IIIB on the basis of surgical pathologic criteria.
5. Confirmation by the local laboratory that the tumour harbours one of the two common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo EGFR mutation resulting in substitution of threonine with methionine at amino acid position 790 in exon 20 of EGFR (T790M) or uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort).
6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.
7. Complete recovery from surgery and standard post-operative therapy (if applicable) at start of study intervention.
8. World Health Organisation Performance Status of 0 to 1.
9. Female participants must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential.
10. Male participants must use effective barrier contraception.

Exclusion Criteria:

1. Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study drug.
2. Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to first dose).
3. Participants who have had only segmentectomies or wedge resections.
4. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer, or other solid tumours curatively treated with no evidence of disease for \> 5 years before the start of study intervention.
5. Treatment with any of the following:

   * Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
   * Pre-operative (neo-adjuvant) platinum-based or other chemotherapy.
   * Any prior anti-cancer or immunological therapy, including investigational therapy, for treatment of NSCLC other than standard platinum-based doublet post-operative adjuvant chemotherapy.
   * Prior treatment with neoadjuvant or adjuvant EGFR tyrosine kinase inhibitor (TKI).
6. 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.
7. Any of the following cardiac criteria:

   * Mean resting corrected QT (QTc) interval \> 470 msec, obtained from 3 electrocardiograms (ECGs).
   * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
   * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
   * Heart failure, congenital long QT interval (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 (TdP).
8. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
9. Inadequate bone marrow reserve or organ function.
10. Women who are breastfeeding.

Primary outcomes:
measure: Estimate the Efficacy of Osimertinib as Measured by Disease Free Survival (DFS) [Common EGFRm Cohort].
timeFrame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 5 years.
Secondary outcomes:
measure: Disease Free Survival Rate at 3, 4 and 5 Years (Uncommon EGFRm Cohort)
timeFrame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years.
measure: DFS Rate at 3 and 4 Years (Common EGFRm Cohort)
timeFrame: From date of first dose until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 5 years. Assessed at 3 years, and 4 years.
measure: Overall Survival (OS) [Common EGFRm Cohort]
timeFrame: From date of first dose until the date of death due to any cause, up to approximately 5 years. Assessed at 3 years, 4 years, and 5 years.
measure: Safety and tolerability in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort)
timeFrame: From date of first dose up to approximately 5 years
measure: Recurrence events in overall population (Common EGFRm Cohort and Uncommon EGFRm Cohort)
timeFrame: From date of first dose up to approximately 5 years
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: White Plains
country: United States
facility: Research Site
state: New York
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Avellino
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Lecce
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Peschiera Del Garda
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Sondrio
country: Italy
facility: Research Site
city: Terni
country: Italy
facility: Research Site
city: Udine
country: Italy
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daejeon
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
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: 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: Seoul
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuantan
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Hualien
country: Taiwan
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Songkhla
country: Thailand
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
References: