Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant NSCLC After First-Line Third-Generation EGFR-TKI Plus Chemotherapy

NCT07822984 | Not Yet Recruiting Phase 2

• 1 other identifier: LUNG-SORT2
• Study Type: interventional
• Target: 374
• Locations: 0 countries
• Sites: N/A

Brief Summary

This national multicenter, randomized controlled clinical trial evaluates the safety and efficacy of consolidative stereotactic radiotherapy in patients with advanced EGFR-mutant non-small cell lung cancer who have oligo-residual disease after four cycles of first-line treatment with third-generation EGFR-TKI plus platinum-based pemetrexed chemotherapy. Eligible participants will be randomized 1:1 to continue third-generation EGFR-TKI plus pemetrexed maintenance therapy alone or to receive stereotactic radiotherapy to all oligo-residual lesions in addition to the same maintenance therapy. The primary endpoint is progression-free survival.

Conditions

SBRT; NSCLC (Advanced Non-small Cell Lung Cancer); EGFR-mutant Non-small Cell Lung Cancer

Keywords

NSCLC; EGFR; TKI; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The time from randomization to disease progression or death of the patient. Patients who have not yet progressed at the time of analysis will be censored at the date of their last contact.

  4 years

Secondary Outcomes (4)

• Overall Survival (OS)

  4 years

• Intracranial Progression-Free Survival (iPFS)

  4 years

• Health-Related Quality of Life (HRQoL)

  4 years

• Incidence of Treatment-Related Toxicities

  4 years

Other Outcomes (1)

• peripheral blood specimens

  4 years

Study Arms (2)

Radiotherapy plus TKI Group

EXPERIMENTAL

Consolidative stereotactic radiotherapy plus continued third-generation EGFR-TKI and pemetrexed maintenance therapy.

Drug: Third-generation EGFR tyrosine kinase inhibitor; Drug: Platinum plus pemetrexed chemotherapy; Drug: Pemetrexed maintenance therapy; Radiation: Consolidative stereotactic radiotherapy

TKI alone Group

ACTIVE COMPARATOR

Continued third-generation EGFR-TKI and pemetrexed maintenance therapy alone.

Drug: Third-generation EGFR tyrosine kinase inhibitor; Drug: Platinum plus pemetrexed chemotherapy; Drug: Pemetrexed maintenance therapy

Interventions

Third-generation EGFR tyrosine kinase inhibitor DRUG

administered during induction and maintenance; the specific third-generation EGFR-TKI is not uniformly restricted in the protocol.

Radiotherapy plus TKI Group; TKI alone Group

Platinum plus pemetrexed chemotherapy DRUG

cisplatin or carboplatin plus pemetrexed for four 3-week cycles during induction.

Radiotherapy plus TKI Group; TKI alone Group

Pemetrexed maintenance therapy DRUG

administered with the third-generation EGFR-TKI until disease progression or unacceptable toxicity.

Radiotherapy plus TKI Group; TKI alone Group

Consolidative stereotactic radiotherapy RADIATION

SRS/SRT/SBRT delivered to all eligible intracranial and/or extracranial oligo-residual lesions, completed as a single course or in staged courses within one month.

Radiotherapy plus TKI Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed non-small cell lung cancer.
• Clinical stage IV disease according to the AJCC 9th edition.
• Sensitizing EGFR mutation: EGFR exon 19 deletion or EGFR L858R.
• Age 18-75 years.
• Karnofsky Performance Status score ≥70.
• Complete whole-body imaging assessment before initiation of first-line third-generation EGFR-TKI plus chemotherapy, with at least one evaluable lesion according to RECIST version 1.1.
• No disease progression after completion of four cycles of first-line third-generation EGFR-TKI plus chemotherapy and no unresolved grade ≥3 nonhematologic toxicity.
• Oligo-residual disease after four treatment cycles, with all residual lesions considered suitable for stereotactic radiotherapy by the investigator.
• Written informed consent.

You may not qualify if:

• Double primary or multiple primary malignancies, except early skin cancer or cervical carcinoma in situ treated with curative intent and without recurrence or progression for at least five years.
• Pregnancy or breastfeeding, or considered unsuitable by the investigator for PET/CT or brain MRI examination.
• History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder that, in the investigator's judgment, may interfere with informed consent or participant compliance.
• Residual lesions considered unsuitable for consolidative stereotactic radiotherapy after first-line third-generation EGFR-TKI plus chemotherapy.

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Platinum

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)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

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: professor

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: September 16, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 16, 2026

Record last verified: 2026-08