Therapy for Advanced NSCLC With EGFR 19delins Mutation

NCT07458919 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: 2025-209
• Study Type: interventional
• Target: 94
• Locations: 0 countries
• Sites: N/A

Brief Summary

In a retrospective analysis of 3,054 advanced NSCLC patients, 41 with EGFR exon 19 deletion-insertions (19delins) received first-generation EGFR TKIs, achieving median PFS of 10.4 months; those with L747\_T751delinsP had notably longer PFS of 18.7 months. Another study of 2,467 treatment-naïve patients found 93 with 19delins treated with first-generation TKIs had median PFS of 19 months, exceeding the 13 months for common 19del mutations. For third-generation TKIs, a study of 215 19delins patients (57 first-line) showed median PFS of 12.9 months, inferior to 23.2 months for common 19del. Our center's retrospective study of 4,666 NSCLC patients in Fujian (2017-2020) included 69 with 19delins: median PFS was 16.7 months with first-generation TKIs versus 7.2 months with third-generation. Evidence suggests specific EGFR deletion locations may affect TKI efficacy; first-generation TKIs may be superior in some 19delins subtypes, while third-generation appear limited. Large prospective data are lacking. This project aims to compare first- versus third-generation EGFR TKIs in 19delins patients via a randomized controlled trial, stratify sensitivity by subtype, and improve survival.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression Free Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

Secondary Outcomes (1)

• OS

  From date of randomization until the date of death from any cause, assessed up to 60 months.

Study Arms (2)

Experimental group

EXPERIMENTAL

First-generation EGFR TKIs, including but not limited to: Icotinib: 125 mg per dose, three times daily Gefitinib: 250 mg per dose, once daily Administration shall be discontinued in case of tumor recurrence or intolerable toxicities during the treatment period.

Drug: Icotinib/Gefitinib

Control group

OTHER

Third-generation EGFR TKIs, including but not limited to: Befotertinib: Oral administration, taken on an empty stomach or with food. 75 mg once daily (QD), 21 days per cycle. After one cycle of treatment, the dose shall be escalated to 100 mg QD if no CTCAE 5.0 grade ≥2 thrombocytopenia or headache occurs; otherwise, 75 mg QD shall be maintained. Osimertinib: 80 mg per dose, once daily Furmonertinib: 80 mg per dose, once daily Administration shall be discontinued in case of tumor recurrence or intolerable toxicities during the treatment period.

Drug: Icotinib/Gefitinib

Interventions

Icotinib/Gefitinib DRUG

To explore the efficacy of first-generation EGFR TKIs versus third-generation EGFR TKIs in the first-line treatment of advanced NSCLC with EGFR 19delins mutation.

Also known as: Befotertinib/Osimertinib/Furmonertinib

Control group; Experimental group

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 locally advanced or metastatic non-small cell lung cancer (NSCLC) (AJCC Cancer Staging Manual, 9th edition, Stage IIIB, IIIC or IV) that is not amenable or suitable for surgical resection or other radical therapies, as assessed by the investigator;
• Epidermal growth factor receptor (EGFR) exon 19 deletion-insertion mutation (19delins) documented by testing of tumor tissue or plasma samples using methods including IHC, NGS, ARMS, etc.;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1;
• No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC;
• Life expectancy ≥ 12 months;
• At least one measurable lesion by imaging in the screening period according to RECIST v1.1;
• Ability to swallow and retain oral medication;
• Adequate organ system function;
• Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of study treatment, and agree to use a medically accepted highly effective method of contraception during the study and for 3 months after the last dose of study drug;
• Voluntary and able to comply with study and follow-up procedures; Ability to understand the nature of the trial and provide written informed consent.

You may not qualify if:

• Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases;
• Active hepatitis B, positive for hepatitis C virus antibody, positive for human immunodeficiency virus (HIV) antibody, or positive for Treponema pallidum antibody;
• Women of childbearing potential with a positive serum pregnancy test within 7 days prior to initiation of treatment, pregnant or lactating women, or male and female subjects who are not using effective contraception or plan to conceive during the entire treatment period and for 3 months after the end of treatment;
• Patients who have used any of the following medications within 14 days prior to the first dose or require concomitant use of such medications during treatment: drugs with a risk of causing QTc prolongation and/or torsade de pointes; strong inhibitors or strong inducers of CYP3A;
• Underwent major surgery or immunotherapy within 4 weeks prior to the first dose; received radiation therapy within 2 weeks prior to the first dose;
• Patients with imaging evidence of tumor invasion of major blood vessels, or those judged to have a very high likelihood of tumor invasion of critical blood vessels leading to fatal massive hemorrhage during the subsequent study period;
• History of interstitial lung disease, drug-induced interstitial disease, or any clinically evident active interstitial lung disease; presence of idiopathic pulmonary fibrosis on baseline CT scan;
• Other severe, acute, or chronic medical conditions that, in the investigator's opinion, may increase the risk associated with study participation or may interfere with the interpretation of study results, including uncontrolled diabetes mellitus, medical or psychiatric illnesses, or laboratory abnormalities;
• Any other conditions deemed by the investigator to make the subject unsuitable for participation in this trial.

Sponsors & Collaborators

• Fuzhou General Hospital: lead

MeSH Terms

Conditions

Lung Neoplasms

Interventions

icotinib; Gefitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yu Zongyang, PhD

  The 900th Hospital of Joint Logistic Support Force PLA

  STUDY DIRECTOR

Central Study Contacts

Yu Zongyang, PhD

CONTACT

13509327806; hxkyzy2024@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2026
• First Posted: March 9, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): October 30, 2030
• Study Completion (Estimated): October 30, 2030
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share