Clinical trial NCT04922138: Aumolertinib Adjuvant Therapy of Resectable Stage I EGFRm+ NSCLC With High-grade Patterns
Official title: Efficacy and Safety of Aumolertinib as Adjuvant Therapy in Resectable Stage I NSCLC With High-grade Patterns and EGFR-sensitizing Mutations (APPOINT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Cancer
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu Hansoh Pharmaceutical Co., Ltd.
First posted: 2021-06-10
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Efficacy and safety of postoperative adjuvant treatment of NSCLC patients with Aumolertinib.

Detailed description: This is a multi-center, two-arm clinical study. In patients with stage I non-squamous non-small cell lung cancer (NSCLC) with EGFR 19del/21L858R with solid, micropapillary, and/or complex gland components ≥10% who have not received any systemic treatment, to evaluate the efficacy and safety of postoperative adjuvant Aumolertinib in NSCLC patients .

Eligibility criteria: Inclusion Criteria:

Any patient who meets all of the following inclusion criteria will qualify for entry into the study:

1. Male or female, aged at least 18 years.
2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology.
3. Brain examination must be done prior to surgery as it is considered standard of care.
4. Patients are pathologically confirmed to be stage I after operation, containing solid, micropapillary, and/or complex gland components ≥10%.
5. Confirmation by the central laboratory that the tumour 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 including T790M.
6. Providing paraffin embedded section(10-15sheets),wax blocks or fresh frozen tissues.
7. 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.
8. World Health Organization Performance Status of 0 to 1.
9. Women of childbearing age should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and should not breastfeed. Before starting the administration, the pregnancy test was negative.
10. Male patients should be willing to use barrier contraception from screening to stopping study treatment for 3 months.(i.e., condoms).
11. For inclusion in study, patient must provide a written informed consent.
12. ≤10 weeks between surgery and treatment period

Exclusion Criteria:

Any patient who meets any of the following exclusion criteria will not qualify for entry into the study:

1. Treatment with any of the following:

   1. Pre-operative or post-operative or planned radiation therapy for the current lung cancer
   2. Pre-operative (neo-adjuvant) platinum based or other chemotherapy
   3. Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
   4. Any other anti-tumor treatment for lung cancer(Including proprietary Chinese patent medicine with anti-tumor effects and anti-tumor immunotherapy, etc.)
   5. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug.
   6. Treatment with an investigational drug within five half-lives of the compound or any of its related material.
   7. Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug..
2. Patients who have had only segmentectomies or wedge resections
3. 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 following the end of treatment.
4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
5. 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).
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 Aumolertinib.
7. Any of the following cardiac criteria:

   1. Mean resting corrected QT interval (QTc) \> 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
   2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \> 250 ms).
   3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, 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.
8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
9. Inadequate bone marrow reserve or organ function.
10. History of hypersensitivity to any active or inactive ingredient of Aumolertinib, or to drugs with a similar chemical structure or class to Aumolertinib.
11. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
12. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
13. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

Primary outcomes:
measure: 2-year Disease free survival (DFS) rate
timeFrame: From date of treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes:
measure: 3-, 4-, and 5-year DFS rate
timeFrame: From date of treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
measure: Overall Survival (OS)
timeFrame: Start of study drug to Survival Endpoint through study completion, an average of 5 years, assessed up to 60 months
measure: Patient health-related quality of life and symptoms (HRQoL) by SF-36v2 Health Survey
timeFrame: From date of treatment start until treatment completion or discontinuation, assessed up to 60 months
Other outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From date of treatment start until 28 days after treatment completion
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: