Neoadjuvant treatment with aumolertinib for lung cancer patients with specific EGFR mutations

Neoadjuvant Aumolertinib in Patients With AI-diagnosed EGFR-mutant High-risk Pulmonary Ground-glass Opacity: A Single-arm, Phase II Trial

This study is testing if aumolertinib can help lung cancer patients with specific EGFR mutations by shrinking their tumors before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Guangzhou Medical University (Academic / other)
• Drugs / interventions: Aumolertinib, chemotherapy, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05946460 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of aumolertinib as a neoadjuvant treatment in patients with AI-diagnosed EGFR-mutant pulmonary ground-glass opacities. Participants will receive aumolertinib for 8 weeks before undergoing surgery to remove the tumor. The study aims to assess the treatment's impact on tumor progression and patient outcomes. Follow-up care will be provided based on the patient's condition after surgery.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with resectable EGFR-mutant pulmonary ground-glass nodules diagnosed by AI.

Not a fit: Patients with prior anti-tumor treatments or those with non-resectable nodules may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve surgical outcomes and overall survival for patients with high-risk lung cancer.

How similar studies have performed: While this approach is novel, similar studies targeting EGFR mutations in lung cancer have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 years old (including 18) and 75 years old (including 75).
2. No prior history of receiving anti-tumor treatment.
3. Presence of at least one resectable malignant EGFR-mutant pulmonary ground-glass nodule diagnosed by AI (CTR ≤ 0.5, EGFR mutation prediction value ≥ 0.82), with a nodule diameter between 0.8-3cm (including both 0.8cm and 3cm).
4. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1.
5. Adequate function of important organs, as follows:

   1. Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelets ≥ 100 × 10\^9/L, hemoglobin ≥ 9 g/dl.
   2. Liver: Bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN.
   3. Kidney: Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 ml/min.
6. Female of childbearing potential must use appropriate contraceptive measures during the study and should not be breastfeeding for at least 3 months after discontinuation of study treatment. Before initiation of treatment, a negative pregnancy test is required, or one of the following criteria should be met to demonstrate no risk of pregnancy:

   1. Postmenopausal is defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
   2. Women under the age of 50 years would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the institution.
   3. Previously undergone irreversible surgical sterilization, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (except for bilateral tubal ligation).
7. Male patients should use barrier contraception (i.e., condoms) from enrollment until 3 months after discontinuation of study treatment.
8. Voluntary participation of the subject and signed informed consent.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. Diagnosis or treatment of any other malignant tumor within the past 5 years (excluding patients with previously resected basal cell carcinoma of the skin or other in situ cancers).
2. Use of systemic anti-tumor treatment, including chemotherapy, radiotherapy, or targeted therapy (including but not limited to monoclonal antibodies, small molecule tyrosine kinase inhibitors), before the study enrollment.
3. Prediction of benign nodules or EGFR wild-type after AI tool assessment of the target lesion.
4. Patient's organ system conditions:

   1. History of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis requiring steroid treatment, or any clinically active interstitial lung disease.
   2. Evidence of interstitial lung disease detected on baseline CT scan.
   3. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or decompensated respiratory, cardiac, hepatic, or renal diseases) as evaluated by the investigator.
   4. Any unstable systemic disease (including active infection, Grade III hypertension, unstable angina, congestive heart failure, hepatic or renal disease, or metabolic disease).
   5. Inability to take oral medications, requirement for parenteral nutrition, previous surgery affecting absorption, or active gastrointestinal ulceration.
   6. Any significant ocular abnormalities, particularly severe dry eye syndrome, severe dry keratoconjunctivitis, severe exposure keratitis, or other conditions that may increase epithelial damage.
   7. History of known neurologic or psychiatric disorders, including epilepsy or dementia.
5. Insufficient bone marrow reserve or organ function, as indicated by the following laboratory values:

   1. Absolute neutrophil count (ANC) \< 1.5 × 10\^9/L.
   2. Platelet count \< 100 × 10\^9/L.
   3. Hemoglobin \< 90 g/L (\< 9 g/dL).
   4. Alanine aminotransferase (ALT) \> 2.5 times the upper limit of normal (ULN).
   5. Aspartate aminotransferase (AST) \> 2.5 times ULN.
   6. Total bilirubin \> 1.5 times ULN.
   7. Serum creatinine \> 1.5 times ULN and creatinine clearance \< 60 mL/min (calculated using the Cockcroft-Gault formula); confirmation of creatinine clearance is only required if creatinine is \> 1.5 times ULN.
6. Women who are either pregnant or breast-feeding.
7. History of hypersensitivity reactions to any active or inactive components of Aumolertinib or drugs with chemical structures similar to Aumolertinib or in the same class.
8. Patients who may have poor compliance with the study procedures and requirements in the investigator's judgment.

Where this trial is running

Guangzhou, Guangdong

• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jianxing He, M.D — The First Affiliated Hospital of Guangzhou Medical University
• Study coordinator: Wenhua Liang, M.D

Conditions Lung Cancer; Aumolertinib; Neoadjuvant Treatment; AI-diagnosed; EGFR-mutant; Ground-glass Opacity