Almonertinib Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB Non-Small Cell Lung Cancer With EGFR-sensitive Mutations

NCT04687241 | Active Not Recruiting Phase 3

• 1 other identifier: HS-10296-302
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the efficacy and safety of Almonertinib versus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm+) stage II-IIIB non-small cell lung cancer (NSCLC), following complete tumor resection with or without adjuvant chemotherapy.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• DFS (Disease free survival) assessed by IRC (Independent Review Committee)

  DFS is defined as the time from randomization to the recurrence of tumor as assessed by IRC or death from any cause on study. The patients will receive long-term follow-up including chest and abdominal CT every 12 weeks during Year 1, then every 24 weeks during Years 2 to 5, and every 48 weeks during Year 6 and onwards; MRI/CT of brain, and bone scan performed every 48 weeks.

  From the time of randomization to recurrence of tumor or death, approximately 4 years.

Secondary Outcomes (6)

• DFS (Disease free survival) assessed by INVs (Investigators)

  From the time of randomization to recurrence of tumor or death, approximately 4 years.

• DFS rate at 2, 3 and 5 years assessed by IRC

  From the time of randomization to recurrence of tumor or death, approximately 6 years.

• OS (Overall survival)

  The time from randomization to death due to any cause, approximately 8 years.

• OS rate at 5 years

  The time from randomization to death due to any cause, approximately 8 years.

• Incidence and severity of adverse events (AEs)

  From the screening period to 28 days after treatment completion, approximately 4 years.

Study Arms (2)

Almonertinib

EXPERIMENTAL

Drug: Almonertinib

Placebo Almonertinib

PLACEBO COMPARATOR

Drug: Placebo Almonertinib

Interventions

Almonertinib DRUG

The initial dose of Almonertinib 110 mg daily can be reduced to 55 mg daily under specific conditions.

Also known as: HS-10296

Almonertinib

Placebo Almonertinib DRUG

Placebo Almonertinib

Placebo Almonertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Provision of informed consent before any study-specific procedures, sampling and analyses.
• \. Male or female, age at least 18 years. 3. Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous histology.
• \. MRI or CT scan of the brain must be done before surgery to exclude brain metastasis.
• \. Complete surgical resection of the primary NSCLC and lymphadenectomy are mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor.
• \. Patients must be classified post-operatively as Stage IIA, IIB, IIIA or IIIB (only T3N2M0) based on pathologic criteria.
• \. Confirmation by the central laboratory that the tumor harbors 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.
• \. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.
• \. A WHO performance status of 0-1 with no deterioration over the past 2 weeks and a minimum life expectancy of 12 weeks.
• \. Female patients should be using adequate contraceptive measures and should not be breastfeeding at the screening period, during the study, and six months after the last dosing of study. A pregnancy test should be done before first dosing unless having evidence of non-child-bearing potential.
• \. Male patients should be willing to use barrier contraception (condoms).

You may not qualify if:

• \. Patients who have had only segmentectomies or wedge resections. 2. Treatment with any of the following:
• Any prior anticancer therapy for the current lung cancer (pre-operative (neoadjuvant) platinum-based or other chemotherapy, pre-operative or post-operative or planned radiation therapy, neoadjuvant or adjuvant EGFR-TKI, other targeted therapy and immunotherapy).
• Major surgery (including primary tumor surgery, excluding placement of vascular access) within 3 weeks of the first dose of study drug.
• Patients currently receiving medications or herbal supplements known to be strong inducers and inhibitors of cytochrome P450 (CYP) 3A4.
• Treatment with an investigational drug within five half-lives of the compound or any of its related material.
• \. Inadequate bone marrow reserve or organ function. 4. Any of the following cardiac criteria:
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• 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).
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., PR interval \> 250 ms).
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure or any concomitant medication known to prolong the QT interval.
• Left ventricular ejection fraction (LVEF) ≤ 40%. 5. History of other malignancies, excluding full treated non-melanoma skin cancer, in-situ cancer, or other solid tumors that hadn't recurrent for \> 5 years following the end of treatment.
• \. 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)).
• \. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of Almonertinib.
• \. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• \. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 except alopecia and Grade 2 prior platinum-therapy related neuropathy.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Jilin Province Cancer Hospital

Changchun, Jilin, 130000, China

Location

Related Publications (1)

• Zhang L, Zhang X, Wu L, Xing W, Liu C, Zhang P, Chen K, Shi J, Xu S, Zhang X, Dong X, Fang H, Yu X, Gao Y, Li G, Chen Z, Fan S, Zhang X, Cheng Y. Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Jan 12:S1470-2045(25)00643-6. doi: 10.1016/S1470-2045(25)00643-6. Online ahead of print.

  PMID: 41539318 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ying Cheng, MD

  Jilin Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 29, 2020
• Study Start: April 30, 2021
• Primary Completion: July 8, 2024
• Study Completion (Estimated): January 1, 2029
• Last Updated: November 7, 2024

Record last verified: 2024-11

Locations

CN (1)