Nebulized Inhalation of Recombinant Human p53 Adenovirus Injection for Treatment of Multiple Ground-Glass Lung Nodules: A Single-Arm Clinical Study

A Single-Arm Clinical Study of Nebulized Inhalation of Recombinant Human p53 Adenovirus Injection (Gendicine) for Treatment of Multiple Ground-Glass Lung Nodules

This study aims to evaluate the safety and efficacy of nebulized inhalation of Recombinant Human Ad-p53 Injection (Gendicine®) for the treatment of multiple ground-glass lung nodules. This is a single-arm, open-label clinical study conducted at The First Affiliated Hospital of Guangzhou Medical University in China. We plan to enroll approximately 38 patients who have been diagnosed with multiple ground-glass nodules. All participants in this study will receive the nebulized Gendicine® treatment. After the treatment, we will monitor changes in the nodules through regular chest CT scans and record any potential treatment-related reactions to determine if this novel therapy is safe and effective. This study has been approved by the hospital's Ethics Committee.

Background: Ground-glass nodules (GGN) are a common manifestation of early-stage lung adenocarcinoma, and their management strategy (active surveillance or surgical intervention) often presents a dilemma for clinicians and patients. Gendicine® (Recombinant Human Ad-p53 Injection) is a gene therapy product approved in China. Previous studies have shown its ability to induce tumor cell apoptosis and enhance the sensitivity to radiotherapy and chemotherapy in various solid tumors. This study aims to investigate this innovative approach of local administration via nebulized inhalation for treating precancerous lesions or early-stage lung cancer.

Methods: This is a single-arm, open-label, phase II clinical trial utilizing the Simon's optimal two-stage design. The first stage plans to enroll 16 patients. If ≥1 objective response (according to RECIST 1.1 criteria) is observed, the study will proceed to the second stage, with a total planned enrollment of 30 evaluable patients (38 subjects will be recruited accounting for a 20% dropout rate). Participants are patients with multiple ground-glass nodules confirmed by imaging, with at least one nodule pathologically confirmed as malignant. The intervention is nebulized inhalation of Gendicine® at a dose of 1×10¹² VP per time, administered once every three days, for a total of four times. The primary endpoint is the Objective Response Rate (ORR), defined as the proportion of patients achieving Complete Response (CR) or Partial Response (PR) at 6 months post-treatment. Secondary endpoints include safety (assessing adverse events according to CTCAE v5.0), changes in tumor markers, and quality of life scores.

Significance: This study is the world's first clinical trial to explore nebulized inhalation of a gene therapy product for the treatment of lung nodules. Positive results would provide a novel, non-invasive treatment strategy for the very early intervention of lung cancer, potentially delaying or preventing nodule malignancy and avoiding surgical trauma.

Inclusion Criteria:

1. Age ≥ 18 years.
2. CT scan confirms the presence of multiple ground-glass nodules (GGNs), with at least one nodule measuring between 0.5 cm and 3.0 cm in diameter.
3. At least one GGN is confirmed as malignant or precancerous (e.g., atypical adenomatous hyperplasia, adenocarcinoma in situ) by histopathology or cytology.
4. Life expectancy ≥ 12 weeks.
5. Adequate pulmonary function tests (FEV1 ≥ 70% of predicted value).
6. Signed informed consent.

Exclusion Criteria:

1. Pregnant or lactating women.
2. History of other active malignancies within the past 5 years.
3. Severe cardiac, hepatic, or renal dysfunction (e.g., NYHA class III/IV heart failure, ALT/AST > 3×ULN, Cr > 1.5×ULN).
4. Uncontrolled systemic infection or immunodeficiency diseases.
5. Participation in another interventional clinical trial within 4 weeks prior to enrollment.
6. Known hypersensitivity to any component of the recombinant human p53 adenovirus injection.