Clinical trial NCT07093762: Efficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
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
Conditions: Non Small Cell Lung Cancer
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.
Interventions:
description: 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.
name: Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel
type: Drug
Study arms:
design_group_description: 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;<br/>2. Confirmed SMARCA4 mutation (by NGS testing);<br/>3. ECOG PS 0-1, with no prior systemic therapy;<br/>4. Absence of driver gene mutations such as EGFR, ALK, or ROS1;<br/>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;<br/>6. Voluntary participation wi
design_group_title: Treatment-naive patients with advanced SMARCA4-mutated NSCLC
Sponsor: 900th Hospital of Joint Logistics Support Force of PLA
Collaborators: 900th Hospital of Joint Logistics Support Force of PLA
Drug name mappings:
name: 白蛋白结合型紫杉醇
lang: CN
name: Albumin-Bound Paclitaxel
lang: EN
name: パクリタキセル(JAN)
lang: JP
name: 卡铂
lang: CN
name: Carboplatin
lang: EN
name: カルボプラチン
lang: JP
name: 阿替利珠单抗
lang: CN
name: Atezolizumab
lang: EN
name: アテゾリズマブ（遺伝子組換え）
lang: JP
name: 贝伐珠单抗
lang: CN
name: Bevacizumab
lang: EN
name: ベバシズマブ（遺伝子組換え）
lang: JP