Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion

Phase 2Not Yet RecruitingNCT07482605

Jiangmen Central Hospital63 enrolled

Overview

This study aims to prospectively and multi-centrally explore the efficacy and safety of furmonertinib combined with upfront thoracic radiotherapy in treating NSCLC participants with EGFR mutations and malignant pleural effusion, thereby providing more evidence-based medical evidence for improved diagnosis and treatment of NSCLC-MPE participants . Additionally, NGS testing of ctDNA from peripheral blood will be performed before the first furmonertinib treatment, before the first thoracic radiotherapy and after its completion, and after disease progression. This will help identify individuals who benefit from this treatment modality and investigate new resistance mechanisms to furmonertinib under the radiotherapy plus TKI combination model, ultimately serving participants better.

This study plans to prospectively and multi-centrally enroll 63 participants with stage IVA non-small cell lung adenocarcinoma harboring EGFR-sensitive mutations (exon 19 deletion, exon 21 L858R mutation) and malignant pleural effusions (MPE). After initial treatment with 2 months of furmonertinib ± thoracentesis and drainage, leading to good control of malignant pleural effusion,participants will receive thoracic radiotherapy (irradiation sites include residual primary lung tumor, regional lymph node metastases, and pleural metastases). Radiation prescription: DT 4000cGy/10F, 4Gy/fraction, once daily, 5 days/week (BED=56Gy, EQD2=46.67Gy, α/β=10). Radiotherapy for bone metastases: 3000cGy/10F, 3Gy/fraction, once daily, 5 days/week. Furmonertinib will be suspended before radiotherapy, during radiotherapy, and for 3 days after completion of radiotherapy. After radiotherapy, furmonertinib maintenance will continue until disease progression or unacceptable toxicity. This study hypothesizes that this treatment modality can effectively control malignant pleural effusion, significantly improve PFS in participants(and potentially OS), and that treatment-related toxicities will be tolerable.Furthermore, by dynamically monitoring ctDNA in peripheral blood using NGS technology before the initial furmonertinib treatment, before and after the first course of thoracic radiotherapy, and after disease progression, the investigators aim to identify individuals suitable for this treatment model and uncover new resistance mechanisms to furmonertinib under the radiotherapy plus TKI combination, thereby guiding clinical practice.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years but ≤ 75 years; 2. Histologically or cytologically confirmed advanced lung adenocarcinoma; 3. Chest CT or whole-body PET-CT indicates pleural invasion with pleural effusion, and pleural fluid cytology confirms the presence of cancer cells. After 2 months of treatment with furmonertinib ± thoracentesis drainage, malignant pleural effusion is controlled (no pleural effusion or only ≤ 100 ml of pleural effusion), and a small amount of pericardial effusion may be present; 4. No prior history of thoracic radiotherapy or thoracic surgery; 5. Positive for EGFR-sensitive mutations (19del/L858R); 6. No prior systemic anti-tumor therapy; 7. ECOG performance status 0-1, with a life expectancy of ≥ 12 weeks; 8. At least one measurable lesion (according to RECIST 1.1); 9. Signed informed consent obtained; 10. No more than 3 bone metastases. Exclusion Criteria: 1. Complicated with interstitial pneumonia or infectious fever before treatment; 2. Complicated with autoimmune diseases or long-term oral corticosteroid use; 3. Prior history of thoracic radiotherapy or thoracic surgery; 4. Complicated with severe anemia, grade 3 WBC or PLT suppression; 5. Allergic to third-generation TKIs; 6. Obvious respiratory symptoms, intolerant to radiotherapy; 7. Active hepatitis B or hepatitis C infection, or currently undergoing antiviral treatment; patients with a clear history of HBV infection whose HBV DNA is at an undetectable level after previous active treatment may be enrolled; 8. Poor control or continuous progression of pleural effusion after two consecutive months of TKI treatment; 9. Patients with brain metastases or liver metastases.

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

PFS defined as time from first dose of furmonertinib to disease progression per RECIST v1.1 or death from any cause, whichever occurs first.

Time frame: From date of first dose to date of first documented disease progression or death from any cause, assessed up to 24 months.

Secondary Outcomes

Overall Response Rate (ORR)

Proportion of subjects achieving complete response (CR) or partial response (PR) according to RECIST v1.1.

Time frame: At 3 months after completion of radiotherapy .

Malignant Pleural Effusion Control Rate .

Proportion of subjects with controlled malignant pleural effusion (complete response + partial response) according to MPE response criteria.

Time frame: At 1, 3, and 6 months after completion of radiotherapy .

Disease Control Rate (DCR)

Proportion of subjects achieving CR, PR, or stable disease (SD) according to RECIST v1.1.

Time frame: At 3 and 6 months after completion of radiotherapy

Overall Survival (OS)

Time from first dose of furmonertinib to death from any cause.

Time frame: From date of first dose to date of death from any cause, assessed up to 36 months .

Incidence of Treatment-Emergent Adverse Events

Frequency, severity, and relationship of adverse events assessed by CTCAE v5.0.

Time frame: From date of first dose to 30 days after last dose .

Peripheral Blood ctDNA Level

Dynamic changes in circulating tumor DNA (ctDNA) concentration in peripheral blood measured by next-generation sequencing (NGS).

Time frame: 48 hours prior to the first furmonertinib treatment, 48 hours prior to the first thoracic radiotherapy, 48 hours after the completion of the last thoracic radiotherapy, and 48 hours after CT indicates disease progression.