FANLUNG-2：The Value of High-Low Mixed-Dose Radiotherapy Combined With Chemo-Immunotherapy Induction in Locally Advanced Non-Small Cell Lung Cancer

NCT07418866 | Not Yet Recruiting Phase 2

• 1 other identifier: 2503317-8
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

Moving immunotherapy ahead of chemoradiotherapy in a "sandwich" model-where tumor reduction is achieved through induction chemo-immunotherapy, immunotherapy is paused during chemoradiotherapy, and then resumed as maintenance post-radiotherapy-has shown promising potential. However, this approach still faces two main challenges: insufficient depth of tumor response and an increased risk of radiation pneumonitis.To address these issues, we investigators have designed a novel high-low mixed-dose irradiation strategy. This approach, combined with two cycles of induction chemo-immunotherapy, aims to achieve rapid tumor regression, improve disease control rates, and reduce overall lung radiation exposure.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  At the end of Cycle 2 chemo- immune therapy (each cycle is 21 days)

Secondary Outcomes (3)

• Tumor Volume Reduction Rate

  At the end of Cycle 2 chemo- immune therapy (each cycle is 21 days)

• PET-CT Negative Conversion Rate

  At the end of Cycle 2 chemo- immune therapy (each cycle is 21 days)

• The incidence of ≥ Grade 2 radiation pneumonitis

  one year

Study Arms (2)

Chemo-immunotherapy + High-Low Mixed-Dose Radiotherapy Group

EXPERIMENTAL

Two cycles of chemo-immunotherapy (Paclitaxel Micelles 100 mg/m²; Cisplatin 30 mg/m²; 5-FU 1200 mg/m²; Serplulimab 200 mg); central ablative radiotherapy: for large masses (short diameter \> 2 cm), the central 1/4 region receives 15-20 Gy/1 fraction, with the 5 Gy isodose line not exceeding the GTV, and maximum doses to the esophagus, trachea, and spinal cord kept below 3 Gy; low-dose radiotherapy: for small masses (short diameter \< 2 cm), 2 Gy/1 fraction. Efficacy evaluation is performed before the third chemotherapy cycle, along with radiotherapy simulation. The fourth chemotherapy cycle is administered concurrently during radiotherapy. Immunotherapy is initiated 1-42 days after radiotherapy completion and maintained for 2 years.

Drug: Paclitaxel Micelles ; Cisplatin ; 5-FU ; Serplulimab; Radiation: High-Low Mixed-Dose Radiotherapy Group

Chemo-immunotherapy Group

ACTIVE COMPARATOR

2 cycles of chemoradiotherapy (Paclitaxel (micellar) 100 mg/m²; Cisplatin 30 mg/m²; 5-Fluorouracil 1200 mg/m²; Serplulimab 200 mg). Efficacy evaluation will be conducted prior to the 3rd chemotherapy cycle, along with radiotherapy simulation. The 4th chemotherapy cycle will be administered concurrently with radiotherapy. Immunotherapy maintenance will begin within 42 days after completion of radiotherapy and continue for 2 years.

Drug: Paclitaxel Micelles ; Cisplatin ; 5-FU ; Serplulimab

Interventions

Paclitaxel Micelles ; Cisplatin ; 5-FU ; Serplulimab DRUG

Paclitaxel Micelles 100 mg/m²; Cisplatin 30 mg/m² ; 5-FU 1200 mg/m²; Serplulimab 200 mg

Chemo-immunotherapy + High-Low Mixed-Dose Radiotherapy Group; Chemo-immunotherapy Group

High-Low Mixed-Dose Radiotherapy Group RADIATION

A high-low mixed-dose irradiation approach: for large lesions (short diameter \> 2 cm), central ablative radiotherapy is applied, delivering a single ablative dose of 15-20 Gy to approximately one-quart

Chemo-immunotherapy + High-Low Mixed-Dose Radiotherapy Group

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent obtained prior to the initiation of any trial-related procedures.
• Age \> 18 years.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Negative for driver gene mutations (EGFR, ALK, ROS1, RET, MET exon 14 skipping, HER2, BRAF, KRAS G12C).
• Locally advanced disease, including Stage III and selected Stage IV (where all lesions are deemed safely treatable with a radiotherapy dose \> 50 Gy in 10 fractions, as assessed by a senior radiation oncologist).
• At least one thoracic lesion with a short-axis diameter \> 2 cm.
• Positive hilar or mediastinal lymph nodes.
• ECOG Performance Status of 0 or 1.
• Life expectancy \> 3 months.
• Adequate organ function, as defined by the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L.
• Platelet count ≥ 100 × 10⁹/L.
• Hemoglobin \> 9 g/dL.
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.

You may not qualify if:

• Patients with severe emphysema, interstitial lung changes, or COPD;
• Resting blood oxygen saturation \< 93%;
• History of other malignancies requiring chemotherapy within the past 2 years;
• History of thoracic radiotherapy;
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatment;
• Current use of systemic corticosteroids (\>10 mg daily prednisone or equivalent) or any form of immunosuppressive therapy within 7 days prior to the first study dose (excluding topical, nasal, inhaled, or local corticosteroids); \*Note: Physiological corticosteroid doses (≤10 mg/day prednisone or equivalent) are permitted.\*
• Known history of allogeneic organ transplantation (except corneal transplant) or allogeneic hematopoietic stem cell transplantation;
• Known allergy to any component of the study drug or its excipients;
• Known history of HIV infection (positive HIV1/2 antibodies);
• Untreated active hepatitis B (defined as HBsAg positive with detectable HBV-DNA above the upper limit of normal at the local laboratory);
• Note: Hepatitis B subjects meeting the following criteria may be enrolled:
• a) HBV DNA \< 1000 copies/mL (200 IU/mL) before the first dose, with ongoing antiviral therapy throughout chemotherapy to prevent reactivation; b) Subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV DNA (-) do not require prophylactic antiviral therapy but require close monitoring for reactivation.
• Active HCV infection (positive HCV antibody with detectable HCV-RNA above the lower limit of detection);
• Administration of live vaccines within 30 days prior to the first dose (Cycle 1, Day 1); Note: Inactivated seasonal influenza vaccines are permitted within 30 days prior to the first dose; live attenuated intranasal influenza vaccines are not allowed.
• Pregnant or breastfeeding women;

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: February 18, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02