Lung CancerEarly Phase 1NCT07458919
Therapy for Advanced NSCLC With EGFR 19delins Mutation
A Early Phase 1 study testing Icotinib/Gefitinib in people with Lung Cancer, run by Fuzhou General Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Icotinib/Gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- No sites listed yet
- Study dates
- 30 Mar 2026to 30 Oct 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Comparative Study on the Efficacy of First-generation Versus Third-generation EGFR TKIs as First-line Therapy for Advanced NSCLC With EGFR Exon 19 Deletion-insertion (19delins) Mutation
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.
Read the detailed description
In a retrospective analysis of 3,054 patients with advanced non-small cell lung cancer (NSCLC), a total of 41 patients with EGFR exon 19 deletion-insertion mutations (19delins) were enrolled, all of whom received first-generation EGFR TKIs. The results showed a median progression-free survival (PFS) of 10.4 months, among which patients with L747_T751delinsP had a median PFS of 18.7 months, which appeared superior to that of patients with other 19delins mutations.
Another retrospective study analyzed 2,467 treatment-naïve patients with locally advanced NSCLC, among whom 93 patients with EGFR exon 19delins mutations were treated with first-generation EGFR TKIs (gefitinib, erlotinib). The median PFS was 19 months in patients with EGFR 19delins mutations, which was longer than that (13 months) in patients with common EGFR 19del mutations treated with first-generation EGFR TKIs during the same period.
However, regarding third-generation EGFR TKIs, a retrospective study enrolled 215 patients with EGFR 19delins mutations, including 57 patients treated with third-generation EGFR TKIs (osimertinib, furmonertinib, aumolertinib) as first-line therapy. The median PFS reached 12.9 months, which was lower than that (23.2 months) in patients with common EGFR 19del mutations.
This result is consistent with our center's previously published findings. A retrospective study of 4,666 NSCLC patients with EGFR mutations in Fujian Province from January 2017 to December 2020 included 69 patients with the EGFR exon 19delins subtype. The median PFS was 16.653 months in patients receiving first-generation EGFR TKIs and 7.179 months in those receiving third-generation EGFR TKIs.
Collectively, available evidence suggests that the specific location and structural variation type of EGFR deletions may affect the efficacy of different generations of TKIs. Especially for rare mutations such as 19delins, first-generation TKIs may show better efficacy in certain subtypes, while the efficacy of third-generation TKIs is relatively limited.
At present, large-scale prospective clinical data are still lacking for this type of mutation, and the optimal targeted therapeutic strategy remains to be further explored.
This project aims to clarify the efficacy and safety of first-generation versus third-generation EGFR TKIs in patients with EGFR exon 19delins mutations through a prospective, randomized controlled trial, further stratify the sensitivity of EGFR TKIs in patients with different EGFR mutation subtypes, and achieve longer survival benefits.
- Conditions
- Lung Cancer
- Being tested
- Icotinib/Gefitinib
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Icotinib/GefitinibDrug
Also called Befotertinib/Osimertinib/Furmonertinib
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Icotinib/Gefitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progression Free Survival
Measured: 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
Overall Survival
Measured: From date of randomization until the date of death from any cause, assessed up to 60 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start30 Mar 2026 (estimated)
- Primary completion30 Oct 2030 (estimated)
- Study completion30 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fuzhou General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yu Zongyang, PhD, Study director, The 900th Hospital of Joint Logistic Support Force PLA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07458919
- Sponsor's protocol ID
- 2025-209
- Status last verified
- Mar 2026
- First submitted
- 1 Mar 2026
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Study on the Efficacy of First-generation Versus Third-generation EGFR TKIs as First-line Therapy for Advanced NSCLC With EGFR Exon 19 Deletion-insertion (19delins) Mutation
- ClinicalTrials.gov ID
- NCT07458919
- Acronym / sponsor ID
- 2025-209
- Conditions
- Lung Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- Fuzhou General HospitalUniversity, hospital or other
- Study start
- 30 Mar 2026 (estimated)
- Primary completion
- 30 Oct 2030 (estimated)
- Study completion
- 30 Oct 2030 (estimated)
- First posted
- 9 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In a retrospective analysis of 3,054 patients with advanced non-small cell lung cancer (NSCLC), a total of 41 patients with EGFR exon 19 deletion-insertion mutations (19delins) were enrolled, all of whom received first-generation EGFR TKIs. The results showed a median progression-free survival (PFS) of 10.4 months, among which patients with L747_T751delinsP had a median PFS of 18.7 months, which appeared superior to that of patients with other 19delins mutations.
Another retrospective study analyzed 2,467 treatment-naïve patients with locally advanced NSCLC, among whom 93 patients with EGFR exon 19delins mutations were treated with first-generation EGFR TKIs (gefitinib, erlotinib). The median PFS was 19 months in patients with EGFR 19delins mutations, which was longer than that (13 months) in patients with common EGFR 19del mutations treated with first-generation EGFR TKIs during the same period.
However, regarding third-generation EGFR TKIs, a retrospective study enrolled 215 patients with EGFR 19delins mutations, including 57 patients treated with third-generation EGFR TKIs (osimertinib, furmonertinib, aumolertinib) as first-line therapy. The median PFS reached 12.9 months, which was lower than that (23.2 months) in patients with common EGFR 19del mutations.
This result is consistent with our center's previously published findings. A retrospective study of 4,666 NSCLC patients with EGFR mutations in Fujian Province from January 2017 to December 2020 included 69 patients with the EGFR exon 19delins subtype. The median PFS was 16.653 months in patients receiving first-generation EGFR TKIs and 7.179 months in those receiving third-generation EGFR TKIs.
Collectively, available evidence suggests that the specific location and structural variation type of EGFR deletions may affect the efficacy of different generations of TKIs. Especially for rare mutations such as 19delins, first-generation TKIs may show better efficacy in certain subtypes, while the efficacy of third-generation TKIs is relatively limited.
At present, large-scale prospective clinical data are still lacking for this type of mutation, and the optimal targeted therapeutic strategy remains to be further explored.
This project aims to clarify the efficacy and safety of first-generation versus third-generation EGFR TKIs in patients with EGFR exon 19delins mutations through a prospective, randomized controlled trial, further stratify the sensitivity of EGFR TKIs in patients with different EGFR mutation subtypes, and achieve longer survival benefits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Icotinib/GefitinibFirst-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. |
| Control group | Other | Drug: Icotinib/GefitinibThird-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Icotinib/GefitinibAlso: Befotertinib/Osimertinib/FurmonertinibTo 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. | Drug | Control group, Experimental group |
Primary outcome
PFS
Time frame: 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.
Progression Free Survival
1 secondary outcome
OS
Time frame: From date of randomization until the date of death from any cause, assessed up to 60 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yu Zongyang, PhD study director
The 900th Hospital of Joint Logistic Support Force PLA
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Icotinib/Gefitinib in people with Lung Cancer, run by Fuzhou General Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yu Zongyang, PhD (13509327806, hxkyzy2024@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.