Non Small Cell Lung CancerNCT07093762
Efficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
An observational study of Non Small Cell Lung Cancer, run by Fuzhou General Hospital at 1 site in China.
Trial summary
SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel
- Type of treatment
- Injection or infusion
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 20 Aug 2025to 30 Jun 2028
- Phase
- Observational
- 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
Study population: Treatment-naive patients with advanced SMARCA4-mutated NSCLC
Who may be able to join
- Patients with pathologically confirmed NSCLC, meeting the following criteria based on the IASLC 9th Edition Lung Cancer TNM Staging System (International Association for the Study of Lung Cancer/Union for International Cancer Control): Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC) disease not amenable to curative-intent concurrent chemoradiotherapy, metastatic, or recurrent (Stage IV) non-squamous NSCLC;
- Confirmed SMARCA4 mutation (verified by NGS testing);
- ECOG performance status 0-1, with no prior systemic anticancer therapy;
- Absence of driver gene mutations (e.g., EGFR, ALK, ROS1);
- Patients capable of providing sufficient blood samples (detailed in sample requirements) and complete baseline clinical data, including: age, gender, smoking history, family history, lesion location(s), lesion size(s), number of lesions, tumor markers, pathological indicators, treatment records, and re-examination/follow-up information;
- Voluntary participation with signed informed consent form, willingness to undergo follow-up assessments and provide treatment process details, efficacy data, and prognostic information, with commitment to complete the entire study.
Who cannot join
- (1) Active autoimmune diseases or interstitial lung disease; (2) Bleeding tendency or contraindications to Bevacizumab.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The 900th Hospital of the Joint Logistic Support Force, PLA, Fuzhou, Fujian, China, 350025
Fuzhou
Zongyang Yu, 13509327806, yuzy527@sina.com
About this study
Official title: Efficacy and Safety Analysis of First-Line ABCP Four-Drug Combination Therapy in Advanced SMARCA4-Mutated Non-Small Cell Lung Cancer: A Multicenter, Single-Arm, Prespecified Subgroup Clinical Trial
SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. 157.7 months, respectively, P=0.001); it is associated with chemotherapy/immunotherapy resistance, rapid progression, and poor prognosis (OS<12 months). Current standard first-line treatments (such as platinum-based chemotherapy ± immunotherapy) have limited efficacy in SMARCA4-mutated patients (ORR<30%, PFS<4 months). Additionally, NapsinA-positive expression can improve the survival of mutated patients (median OS: 32 months vs. 15 months, P=0.033), but this effect exists only in the SMARCA4-mutated group.
The ABCP regimen has a synergistic mechanism: Atezolizumab (anti-PD-L1): reverses the immunosuppressive microenvironment; Bevacizumab (anti-VEGF): inhibits angiogenesis and enhances T-cell infiltration; Platinum + Paclitaxel: directly kill tumor cells and release neoantigens. Therefore, the investigators preset that SMARCA4 mutation may affect chemotherapy/immunotherapy response through epigenetic regulation, and its value as a predictive biomarker needs to be validated. Hence, the purpose of this study is to observe and explore the efficacy and safety of first-line ABCP four-drug combination therapy in patients with advanced SMARCA4-mutated non-small cell lung cancer.
Read the detailed description
SMARCA4 is the core catalytic subunit of the SWI/SNF chromatin remodeling complex, and its loss-of-function mutations are closely associated with the development of lung cancer and poor prognosis. Studies show that SMARCA4 mutations account for approximately 5-10% of advanced NSCLC, are more common in males and smokers, and have a significantly higher incidence in large cell carcinoma (LCC) than in other histological subtypes (51.4% in LCC). Data from Asian cohorts show that SMARCA4 mutations are mutually exclusive with driver gene mutations such as EGFR and ALK, and are often accompanied by high tumor mutational burden (TMB) and low PD-L1 expression.
SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. 157.7 months, respectively, P=0.001); it is associated with chemotherapy/immunotherapy resistance, rapid progression, and poor prognosis (OS<12 months). Current standard first-line treatments (such as platinum-based chemotherapy ± immunotherapy) have limited efficacy in SMARCA4-mutated patients (ORR<30%, PFS<4 months). Additionally, NapsinA-positive expression can improve the survival of mutated patients (median OS: 32 months vs. 15 months, P=0.033), but this effect exists only in the SMARCA4-mutated group.
Currently, there are no targeted drugs directly against SMARCA4 mutations, and sensitivity to platinum-based chemotherapy is low. However, the high TMB signature suggests that some patients may benefit from immunotherapy combined with chemotherapy (e.g., the 5-year OS rate with camrelizumab combined with chemotherapy reached 27.8%). SMARCA4 mutation is associated with low PD-L1 expression and reduced CD8+ T-cell infiltration, but high TMB may suggest potential benefit from immunotherapy.
The ABCP regimen has a synergistic mechanism: Atezolizumab (anti-PD-L1): reverses the immunosuppressive microenvironment; Bevacizumab (anti-VEGF): inhibits angiogenesis and enhances T-cell infiltration; Platinum + Paclitaxel: directly kill tumor cells and release neoantigens. Therefore, the investigators preset that SMARCA4 mutation may affect chemotherapy/immunotherapy response through epigenetic regulation, and its value as a predictive biomarker needs to be validated. Hence, the purpose of this study is to observe and explore the efficacy and safety of first-line ABCP four-drug combination therapy in patients with advanced SMARCA4-mutated non-small cell lung cancer.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel
- Keywords
- SMARCA4, NSCLC, treatment efficacy, biomarker
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab+Bevacizumab+Carboplatin+PaclitaxelDrug
Atezolizumab: 1200 mg IV every 3 weeks; Bevacizumab: 15 mg/kg IV every 3 weeks; Carboplatin: AUC 5 IV every 3 weeks; Paclitaxel: 175 mg/m² IV every 3 weeks. Treatment cycles: After 4-6 cycles, continue Atezolizumab + Bevacizumab as maintenance therapy until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Treatment-naive patients with advanced SMARCA4-mutated NSCLC | 1. Patients pathologically confirmed as having NSCLC, with histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC) that is not amenable to curative-intent concurrent chemoradiotherapy, metastatic, or recurrent (Stage IV) non-squamous NSCLC, staged according to the IASLC 9th Edition Lung Cancer TNM Staging System by the International Association for the Study of Lung Cancer and the Union for International Cancer Control;
2. Confirmed SMARCA4 mutation (by NGS testing);
3. ECOG PS 0-1, with no prior systemic therapy;
4. Absence of driver gene mutations such as EGFR, ALK, or ROS1;
5. Patients who can provide sufficient blood samples (see sample requirements for details) and complete basic clinical data, including age, gender, smoking history, family history, lesion location(s), lesion size(s), number of lesions, tumor markers, pathological indicators, treatment information, and re-examination/follow-up information;
6. Voluntary participation wi Receives: Drug: Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective Response Rate (ORR): Assessed according to RECIST v1.1 criteria to evaluate the antitumor activity of the ABCP regimen.
Measured: through study completion, an average of 1 year
Progression-Free Survival
Progression-Free Survival (PFS): Defined as the time from enrollment to disease progression or death.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2025
- Study start20 Aug 2025 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fuzhou General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- 900th Hospital of PLA Joint Logistic Support Force
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07093762
- Sponsor's protocol ID
- 2025-059
- Status last verified
- Jul 2025
- First submitted
- 29 Jun 2025
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Analysis of First-Line ABCP Four-Drug Combination Therapy in Advanced SMARCA4-Mutated Non-Small Cell Lung Cancer: A Multicenter, Single-Arm, Prespecified Subgroup Clinical Trial
- ClinicalTrials.gov ID
- NCT07093762
- Acronym / sponsor ID
- 2025-059
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- SMARCA4, NSCLC, treatment efficacy, biomarker
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Fuzhou General HospitalUniversity, hospital or other
- Collaborators
- 900th Hospital of PLA Joint Logistic Support Force
- Study start
- 20 Aug 2025 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 30 Jul 2025 (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.
SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. 157.7 months, respectively, P=0.001); it is associated with chemotherapy/immunotherapy resistance, rapid progression, and poor prognosis (OS<12 months). Current standard first-line treatments (such as platinum-based chemotherapy ± immunotherapy) have limited efficacy in SMARCA4-mutated patients (ORR<30%, PFS<4 months). Additionally, NapsinA-positive expression can improve the survival of mutated patients (median OS: 32 months vs. 15 months, P=0.033), but this effect exists only in the SMARCA4-mutated group.
The ABCP regimen has a synergistic mechanism: Atezolizumab (anti-PD-L1): reverses the immunosuppressive microenvironment; Bevacizumab (anti-VEGF): inhibits angiogenesis and enhances T-cell infiltration; Platinum + Paclitaxel: directly kill tumor cells and release neoantigens. Therefore, the investigators preset that SMARCA4 mutation may affect chemotherapy/immunotherapy response through epigenetic regulation, and its value as a predictive biomarker needs to be validated. Hence, the purpose of this study is to observe and explore the efficacy and safety of first-line ABCP four-drug combination therapy in patients with advanced SMARCA4-mutated non-small cell lung cancer.
Detailed description
SMARCA4 is the core catalytic subunit of the SWI/SNF chromatin remodeling complex, and its loss-of-function mutations are closely associated with the development of lung cancer and poor prognosis. Studies show that SMARCA4 mutations account for approximately 5-10% of advanced NSCLC, are more common in males and smokers, and have a significantly higher incidence in large cell carcinoma (LCC) than in other histological subtypes (51.4% in LCC). Data from Asian cohorts show that SMARCA4 mutations are mutually exclusive with driver gene mutations such as EGFR and ALK, and are often accompanied by high tumor mutational burden (TMB) and low PD-L1 expression.
SMARCA4 mutation is clinically known to be an independent poor prognostic factor. Both TCGA and the investigators institution's preliminary research indicate that the median overall survival (OS) of mutated patients is significantly shorter than that of wild-type patients (32 months vs. 157.7 months, respectively, P=0.001); it is associated with chemotherapy/immunotherapy resistance, rapid progression, and poor prognosis (OS<12 months). Current standard first-line treatments (such as platinum-based chemotherapy ± immunotherapy) have limited efficacy in SMARCA4-mutated patients (ORR<30%, PFS<4 months). Additionally, NapsinA-positive expression can improve the survival of mutated patients (median OS: 32 months vs. 15 months, P=0.033), but this effect exists only in the SMARCA4-mutated group.
Currently, there are no targeted drugs directly against SMARCA4 mutations, and sensitivity to platinum-based chemotherapy is low. However, the high TMB signature suggests that some patients may benefit from immunotherapy combined with chemotherapy (e.g., the 5-year OS rate with camrelizumab combined with chemotherapy reached 27.8%). SMARCA4 mutation is associated with low PD-L1 expression and reduced CD8+ T-cell infiltration, but high TMB may suggest potential benefit from immunotherapy.
The ABCP regimen has a synergistic mechanism: Atezolizumab (anti-PD-L1): reverses the immunosuppressive microenvironment; Bevacizumab (anti-VEGF): inhibits angiogenesis and enhances T-cell infiltration; Platinum + Paclitaxel: directly kill tumor cells and release neoantigens. Therefore, the investigators preset that SMARCA4 mutation may affect chemotherapy/immunotherapy response through epigenetic regulation, and its value as a predictive biomarker needs to be validated. Hence, the purpose of this study is to observe and explore the efficacy and safety of first-line ABCP four-drug combination therapy in patients with advanced SMARCA4-mutated non-small cell lung cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment-naive patients with advanced SMARCA4-mutated NSCLC | – | Drug: Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel1. Patients pathologically confirmed as having NSCLC, with histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC) that is not amenable to curative-intent concurrent chemoradiotherapy, metastatic, or recurrent (Stage IV) non-squamous NSCLC, staged according to the IASLC 9th Edition Lung Cancer TNM Staging System by the International Association for the Study of Lung Cancer and the Union for International Cancer Control; 2. Confirmed SMARCA4 mutation (by NGS testing); 3. ECOG PS 0-1, with no prior systemic therapy; 4. Absence of driver gene mutations such as EGFR, ALK, or ROS1; 5. Patients who can provide sufficient blood samples (see sample requirements for details) and complete basic clinical data, including age, gender, smoking history, family history, lesion location(s), lesion size(s), number of lesions, tumor markers, pathological indicators, treatment information, and re-examination/follow-up information; 6. Voluntary participation wi |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Treatment-naive patients with advanced SMARCA4-mutated NSCLC
Key inclusion criteria (6 listed)
- Patients with pathologically confirmed NSCLC, meeting the following criteria based on the IASLC 9th Edition Lung Cancer TNM Staging System (International Association for the Study of Lung Cancer/Union for International Cancer Control): Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC) disease not amenable to curative-intent concurrent chemoradiotherapy, metastatic, or recurrent (Stage IV) non-squamous NSCLC;
- Confirmed SMARCA4 mutation (verified by NGS testing);
- ECOG performance status 0-1, with no prior systemic anticancer therapy;
- Absence of driver gene mutations (e.g., EGFR, ALK, ROS1);
- Patients capable of providing sufficient blood samples (detailed in sample requirements) and complete baseline clinical data, including: age, gender, smoking history, family history, lesion location(s), lesion size(s), number of lesions, tumor markers, pathological indicators, treatment records, and re-examination/follow-up information;
Key exclusion criteria (1 listed)
- (1) Active autoimmune diseases or interstitial lung disease; (2) Bleeding tendency or contraindications to Bevacizumab.
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 |
|---|---|---|
| Atezolizumab+Bevacizumab+Carboplatin+PaclitaxelAtezolizumab: 1200 mg IV every 3 weeks; Bevacizumab: 15 mg/kg IV every 3 weeks; Carboplatin: AUC 5 IV every 3 weeks; Paclitaxel: 175 mg/m² IV every 3 weeks. Treatment cycles: After 4-6 cycles, continue Atezolizumab + Bevacizumab as maintenance therapy until disease progression or unacceptable toxicity. | Drug | Treatment-naive patients with advanced SMARCA4-mutated NSCLC |
Primary outcome
Objective Response Rate
Time frame: through study completion, an average of 1 year
Objective Response Rate (ORR): Assessed according to RECIST v1.1 criteria to evaluate the antitumor activity of the ABCP regimen.
Progression-Free Survival
Time frame: through study completion, an average of 1 year
Progression-Free Survival (PFS): Defined as the time from enrollment to disease progression or death.
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 30 Jul 2025.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non Small Cell Lung Cancer, run by Fuzhou General Hospital at 1 site in China.
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 6 inclusion and 1 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 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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 Zongyang Yu (13509327806, yuzy527@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. 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 30 Jul 2025.