A Phase II Study of Anlotinib and Platinum-Based Chemotherapy in Patients With SMARCA4-Deficient, Locally Advanced or Metastatic Lung Cancer.

NCT07307443 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCC5896
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of combining Anlotinib with platinum-based chemotherapy for treating locally advanced or advanced lung cancer in patients whose tumors are characterized by SMARCA4 deficiency, as evidenced by the loss of BRG1 protein via immunohistochemistry (IHC). It will also learn about the safety of this combination treatment. The main questions it aims to answer are:

1. 1.How long can this treatment delay the worsening of the cancer (Progression-Free Survival, PFS)?
2. 2.What side effects or medical problems do participants have when taking this combination? This is a single-arm study, meaning all participants will receive the same investigational combination therapy. Researchers will monitor how well the cancer responds and compare the results to historical data from similar patients who received other treatments.
3. 3.Receive treatment in 21-day cycles: take Anlotinib pills on days 1-14 of each cycle and receive platinum-based chemotherapy by intravenous infusion on day 1 (or days 1 and 8).
4. 4.Undergo regular clinic visits for imaging scans (like CT scans), blood tests, and physical examinations to check the cancer's status and their overall health.
5. 5.Complete questionnaires about their quality of life.
6. 6.Provide tumor tissue and blood samples for exploratory research to understand which patients might benefit most from this treatment.

Conditions

SMARCA4-Deficient Tumor; Locally Advanced or Metastatic Lung Cancer

Keywords

SMARCA4-Deficient Locally advanced or Metastatic Lung Cancer; first line therapy; combination therapy; Anlotinib; Platinum-based chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the first dose of study treatment to the first documentation of disease progression according to RECIST v1.1 (as assessed by investigators) or death from any cause, whichever occurs first. Subjects who are alive without progression at the time of analysis will be censored at the date of the last tumor assessment.

  From enrollment to the end of monitoring at 2 years.

Secondary Outcomes (6)

• Overall Survival (OS)

  From enrollment to the end of monitoring at 2 years.

• Objective Response Rate (ORR)

  From enrollment to the end of monitoring at 2 years.

• Duration of Response (DoR)

  From enrollment to the end of monitoring at 2 years.

• Disease Control Rate (DCR)

  From enrollment to the end of monitoring at 2 years.

• The incidence of adverse events

  From enrollment to the end of monitoring at 2 years

Other Outcomes (1)

• Biomarker Discovery

  From enrollment to the end of monitoring at 2 years

Study Arms (1)

combined treatment group

EXPERIMENTAL

This study evaluates a first-line treatment for locally advanced or metastatic SMARCA4-deficient lung cancer, combining Anlotinib-an oral multi-target tyrosine kinase inhibitor that primarily inhibits tumor angiogenesis-with platinum-based chemotherapy. The rationale for this combination is to integrate potent anti-angiogenic therapy with standard cytotoxic chemotherapy, aiming to address the limited efficacy of current standard therapies in this aggressive molecular subset. Patients receive the combination of Anlotinib and platinum-doublet chemotherapy for 4-6 induction cycles, followed by Anlotinib monotherapy as maintenance treatment until disease progression or unacceptable toxicity. This design aims to maximize disease control while balancing long-term treatment tolerability. No prior prospective clinical studies have specifically evaluated this regimen in patients with SMARCA4-deficient NSCLC confirmed by BRG1 protein loss.

Drug: Anlotinib, nab-paclitaxel, carboplatin

Interventions

Anlotinib, nab-paclitaxel, carboplatin DRUG

Participants will receive Anlotinib (12 mg, orally, once daily on days 1-14) in combination with nab-paclitaxel (260 mg/m², IV, administered as a single dose on day 1 or split between days 1 and 8) and carboplatin (AUC=4-5, IV, day 1) every 21 days for 4-6 induction cycles. Dose adjustments may be made based on clinical judgment and tolerability. Patients who do not experience disease progression or intolerable toxicity following the induction phase will proceed to maintenance therapy with Anlotinib monotherapy (12 mg, orally, once daily on days 1-14 every 21 days). Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, investigator decision, loss to follow-up, death, or meeting other protocol-defined criteria for discontinuation. The maximum duration of Anlotinib treatment is 24 months. Beyond this period, continuation will be at the investigator's discretion based on an individual benefit-risk assessment.

combined treatment group

Eligibility Criteria

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

You may qualify if:

• Patients must meet ALL the following criteria to be eligible for trial participation:
• Voluntary participation and provision of written informed consent.
• Age ≥ 18 years.
• Life expectancy ≥ 3 months.
• Diagnosed with unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) lung cancer not amenable to curative radiotherapy.
• Tumor confirmed by immunohistochemistry (IHC) to be deficient in the BRG1 protein (encoded by the SMARCA4 gene).
• No prior systemic anti-cancer therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Willing and able to provide archival or fresh tumor tissue samples from primary or metastatic sites for biomarker analysis. Enrollment may be considered after investigator assessment if tissue is unavailable, provided all other criteria are met.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Adequate organ and bone marrow function as defined by the following laboratory values (within screening period):
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L. 10.2. Platelet count ≥ 100 × 10⁹/L. 10.3. Hemoglobin ≥ 90 g/L (without blood transfusion within 14 days). 10.4. Serum creatinine ≤ 1 × Upper Limit of Normal (ULN) OR estimated creatinine clearance \> 50 mL/min (Cockcroft-Gault formula).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present).
• Total bilirubin ≤ 1.5 × ULN (For subjects with Gilbert's syndrome, total bilirubin must be \< 51.3 µmol/L).
• Prothrombin time (PT), activated partial thromboplastin time (APTT), and International Normalized Ratio (INR) ≤ 1.5 × ULN (for subjects not receiving anticoagulant therapy).

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from the trial:
• Pathological diagnosis containing a small cell carcinoma component.
• Symptomatic brain metastases.
• Leptomeningeal carcinomatosis.
• Conditions that compromise intravenous access or oral drug administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction); OR unwillingness or inability to undergo a repeat biopsy or provide sufficient tissue samples for comprehensive analysis (whole-exome sequencing, transcriptome sequencing, multiplex fluorescence immunohistochemistry).
• Failure to recover from adverse reactions of prior therapies to ≤ Grade 1 per CTCAE v5.0, except for toxicities deemed by the investigator to pose no safety risk (e.g., Grade 2 alopecia, Grade 2 peripheral neuropathy, Grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, or stable hypothyroidism on hormone replacement therapy).
• Major surgical procedure, significant traumatic injury within 4 weeks prior to the first dose, or anticipated need for major surgery during the study treatment period (unless specified in the protocol); OR presence of non-healing wounds or fractures. (Major surgery is defined as Grade 3 or higher according to the National Surgery Classification Catalog 2022 edition).
• Any arterial or venous thromboembolic event (e.g., cerebrovascular accident, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 6 months prior to the first dose; OR any bleeding or hemorrhagic event ≥ Grade 3 per CTCAE v5.0 within 4 weeks prior to the first dose.
• Poorly controlled active viral hepatitis. Eligible subjects meeting the following criteria may be screened:
• HBsAg-positive subjects must have HBV DNA \< 2000 IU/mL (or 1×10⁴ copies/mL) OR have received at least 1 week of anti-HBV therapy prior to study initiation with at least a 10-fold (1-log) reduction in viral load, AND agree to receive continuous anti-HBV therapy throughout the study.
• HCV-infected subjects (HCV Ab or HCV RNA positive) must be in a stable condition as judged by the investigator OR be receiving approved antiviral therapy at enrollment and willing to continue it during the study.
• History of psychotropic substance abuse with inability to abstain, or presence of psychiatric disorders.
• Prior or planned allogeneic bone marrow transplantation or solid organ transplantation.
• History of hepatic encephalopathy.
• Significant cardiovascular disease, including any of the following:

Sponsors & Collaborators

• Zhijie Wang: lead
• Hebei Medical University Fourth Hospital: collaborator
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (1)

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

anlotinib; 130-nm albumin-bound paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Central Study Contacts

Zhijie Wang, MD

CONTACT

+86 13466323860; jie_969@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: December 29, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)