Efficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC

NCT07093762 | Not Yet Recruiting DMC FDA Drug

• 1 other identifier: 2025-059
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Non Small Cell Lung Cancer

Keywords

SMARCA4; NSCLC; treatment efficacy; biomarker

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  Objective Response Rate (ORR): Assessed according to RECIST v1.1 criteria to evaluate the antitumor activity of the ABCP regimen.

  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.

  through study completion, an average of 1 year

Study Arms (1)

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

Drug: Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel

Interventions

Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel DRUG

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.

Treatment-naive patients with advanced SMARCA4-mutated NSCLC

Eligibility Criteria

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

Study Population

Treatment-naive patients with advanced SMARCA4-mutated NSCLC

You may qualify if:

• 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.

You may not qualify if:

• (1) Active autoimmune diseases or interstitial lung disease; (2) Bleeding tendency or contraindications to Bevacizumab.

Sponsors & Collaborators

• Fuzhou General Hospital: lead
• 900 Hospital of Joint Logistics Support Force of PLA: collaborator

Study Sites (1)

The 900th Hospital of the Joint Logistic Support Force, PLA, Fuzhou, Fujian, China, 350025

Fuzhou, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Zongyang Yu

CONTACT

13509327806; yuzy527@sina.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2025
• First Posted: July 30, 2025
• Study Start: August 20, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)