Furmonertinib Plus Radiotherapy for EGFR+ NSCLC With Pleural Effusion

NCT07482605 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025 312 号 B
• Study Type: interventional
• Target: 63
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed as a prospective, multi-center investigation to explore the efficacy and safety of furmonertinib combined with upfront thoracic radiotherapy with or without metastatic lesion radiotherapy in subjects with EGFR-mutant NSCLC and malignant pleural effusion (MPE), aiming to provide additional evidence-based medical support for optimizing the management of NSCLC-MPE subjects. In addition, peripheral blood ctDNA next-generation sequencing (NGS) will be performed at two time points-before the first furmonertinib treatment and one month after the completion of thoracic radiotherapy-to identify subpopulations most likely to benefit from this therapeutic approach and to elucidate resistance mechanisms specific to the radiotherapy-plus-furmonertinib combination, ultimately facilitating more personalized care for these subjects.

Conditions

Lung Cancer (NSCLC); Malignant Pleural Effusions (Mpe)- Pleurodesis

Keywords

Furmonertinib; Radiotherapy; EGFR mutation; Lung adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.

• Malignant pleural effusion recurrence rate

  Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.

• Disease Control Rate (DCR)

  Evaluations are performed at 1 month post-radiotherapy, and subsequently every 3 months, with a total follow-up period of 18 months.

• Overall Survival (OS)

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

• Adverse event

  From date of first dose to 30 days after last dose .

Study Arms (1)

experimental

EXPERIMENTAL

Subjects will receive an initial 10-12 weeks of furmonertinib therapy with or without therapeutic thoracentesis to achieve adequate control of malignant pleural effusion, followed by thoracic radiotherapy targeting residual primary pulmonary lesions, regional lymph node metastases, and pleural metastatic lesions, with or without radiotherapy to osseous, adrenal, hepatic, or brain metastases. Oral furmonertinib will be withheld before, during, and for 3 days after radiotherapy. Resumption of furmonertinib maintenance will occur 3 days after radiotherapy completion and continue until disease progression or unacceptable toxicity.

Drug: Furmonertinib; Radiation: Thoracic Radiotherapy (TRT)

Interventions

Furmonertinib DRUG

Subjects will receive furmonertinib 80 mg orally once daily. The drug will be suspended before radiotherapy initiation, maintained on hold during the entire radiotherapy course, and withheld for an additional 3 days after radiotherapy ends, after which it will be resumed.

experimental

Thoracic Radiotherapy (TRT) RADIATION

The radiotherapy target volume encompasses residual primary pulmonary lesions, regional lymph node metastases, and pleural metastases, with the option to additionally irradiate osseous, adrenal, hepatic, or brain metastases (with a maximum of 6 total irradiated sites and no more than 3 involved organs). Consolidative cranial irradiation for brain metastases will be deferred in cases where the residual lesion diameter is \<1 cm following furmonertinib therapy and the patient remains free of clinically significant neurological symptoms.

experimental

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Histologically or cytologically confirmed advanced lung adenocarcinoma.
• Unlimited number of metastatic lesions, but with involvement of no more than 3 organs.
• Previously untreated, clinical stage IV disease per AJCC/UICC 9th edition.
• Presence of pleural effusion as indicated by chest CT or ultrasound; cytological confirmation of malignant cells in the pleural effusion is preferred. If malignant cells are not detected in the pleural effusion, chest CT with contrast or whole-body PET/CT must demonstrate unequivocal pleural nodular metastases.
• After 8-10 weeks of furmonertinib therapy with or without therapeutic thoracentesis, the overall radiographic response is assessed as effective (CR + PR + SD), and malignant pleural effusion is adequately controlled (defined as no pleural effusion or only minimal pleural effusion on ultrasound or chest CT: maximum depth \< 3 cm, estimated volume \< 500 mL). Concurrent minimal pericardial effusion is permissible (defined as maximum diastolic width \< 1 cm on echocardiography, estimated volume \< 100 mL).
• No prior thoracic radiotherapy.
• Positive for EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R).
• No prior systemic anticancer therapy.
• ECOG performance status 0-2, with a life expectancy of ≥ 12 weeks.
• At least one measurable lesion per RECIST 1.1.
• Adequate bone marrow function to tolerate anticancer treatment: WBC ≥ 3 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 75 × 10⁹/L, and absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L.
• Essentially normal hepatic and renal function:
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL/min;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN is acceptable in patients with liver metastases);

You may not qualify if:

• Pre-existing interstitial lung disease (ILD) or infectious fever prior to treatment.
• Radiographic progression (PD) after 8-10 weeks of TKI therapy, or development of grade ≥ 2 ILD.
• Concurrent autoimmune disease requiring long-term oral corticosteroid therapy.
• Severe anemia.
• Known hypersensitivity to furmonertinib.
• Significant respiratory symptoms (e.g., chest tightness, cough) that preclude tolerance to radiotherapy.
• Active hepatitis B or C virus infection with concomitant grade \> 2 hepatic impairment. Patients may be considered eligible if liver function recovers to grade 1 after active hepatoprotective therapy and antiviral treatment.
• Poorly controlled or continuously progressive pleural effusion after 8-10 weeks of furmonertinib therapy.
• Symptomatic brain metastases.

Sponsors & Collaborators

• Jiangmen Central Hospital: lead

Related Publications (6)

• Li Q, Hu C, Su S, Ma Z, Geng Y, Hu Y, Jin H, Li H, Lu B. Impact of thoracic tumor radiotherapy on survival in non-small-cell lung cancer with malignant pleural effusion treated with targeted therapy: Propensity score matching study. Cancer Med. 2023 Jul;12(14):14949-14959. doi: 10.1002/cam4.6130. Epub 2023 Jun 8.

  PMID: 37288833 BACKGROUND

• Li W, Wu P, Liang Z, Li L, Chen Y, Zhang W, Zhang H, Fang C. Efficacy and safety of tyrosine kinase inhibitors with thoracic radiotherapy for patients with oncogene-mutated non-small cell lung cancer: a meta-analysis. Radiat Oncol. 2024 Nov 6;19(1):154. doi: 10.1186/s13014-024-02538-y.

  PMID: 39506792 BACKGROUND

• Hibino M, Hiranuma O, Takemura Y, Katayama Y, Chihara Y, Harada T, Fujita K, Kita T, Tamiya N, Tsuda T, Shiotsu S, Tamura Y, Aoyama T, Nakamura Y, Terashima M, Morimoto Y, Nagata K, Yoshimura K, Uchino J, Takayama K. Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial. JTO Clin Res Rep. 2022 Oct 15;3(12):100424. doi: 10.1016/j.jtocrr.2022.100424. eCollection 2022 Dec.

  PMID: 36438852 BACKGROUND

• Nokihara H, Ogino H, Mitsuhashi A, Kondo K, Ogawa E, Ozaki R, Yabuki Y, Yoneda H, Otsuka K, Nishioka Y. Efficacy of osimertinib in epidermal growth factor receptor-mutated non-small-cell lung cancer patients with pleural effusion. BMC Cancer. 2022 Jun 1;22(1):597. doi: 10.1186/s12885-022-09701-2.

  PMID: 35650550 BACKGROUND

• Kiritani A, Amino Y, Uchibori K, Akita T, Harutani Y, Ogusu S, Tsugitomi R, Manabe R, Ariyasu R, Kitazono S, Yanagitani N, Nishio M. Efficacy of osimertinib in patients with EGFR-mutation positive non-small cell lung cancer with malignant pleural effusion. Thorac Cancer. 2024 Feb;15(5):402-409. doi: 10.1111/1759-7714.15210. Epub 2024 Jan 16.

  PMID: 38226415 BACKGROUND

• Li Q, Hu C, Su S, Ma Z, Geng Y, Hu Y, Li H, Lu B. Failure pattern and radiotherapy exploration in malignant pleural effusion non-small cell lung cancer treated with targeted therapy. Front Oncol. 2023 May 19;13:974735. doi: 10.3389/fonc.2023.974735. eCollection 2023.

  PMID: 37274290 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pleural Effusion, Malignant; Adenocarcinoma of Lung

Interventions

aflutinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pleural Neoplasms; Pleural Effusion; Pleural Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Masking Description
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of the Oncology Department

Model Details: Model Description

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 19, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: July 17, 2026

Record last verified: 2026-07