Furmonertinib Combined With Anlotinib in Lung Adenocarcinoma Patients With EGFR Mutations and Brain Metastases (LungBrain001)

Furmonertinib Combined With Anlotinib in Lung Adenocarcinoma Patients With EGFR Mutations and Brain Metastases, a Prospective Phase II Single-arm Clinical Study

The goal of this clinical trial is to learn if furmonertinib plus anlotinib works to treat participants with lung adenocarcinoma with EGFR mutations and brain metastases. It will also learn about the safety of furmonertinib plus anlotinib. The main questions it aims to answer are:

• Does furmonertinib plus anlotinib increase the number of participants who has a significant tumor shrinkage?
• What medical problems do participants have when taking furmonertinib plus anlotinib? Researchers will evaluate the safety and efficacy of furmonertinib plus anlotinib.

Participants will:

• Take furmonertinib(every day) and anlotinib(two weeks on and one week off)
• Visit the clinic once every 3 weeks for checkups and tests.
• Keep a diary of their symptoms.

Study Overview

• Status: Not yet recruiting
• Conditions: Adenocarcinoma of Lung Metastatic to Brain
• Intervention / Treatment: Drug: Furmonertinib; Drug: Anlotinib

Detailed Description

The objective of this study is to explore the effectiveness and safety of furmonertinib and anlotinib as first-line treatment for patients with EGFR mutation and brain metastasis lung adenocarcinoma.

This clinical trial adopts a single-center, prospective, single-arm phase II trial design. Each 3 weeks constitute a treatment cycle until disease progression or intolerance.

After screening, eligible patients will be enrolled in the study. They will receive furmonertinib and anlotinib as first-line treatment. The patients will undergo regular visits, and researchers will collect data on efficacy and safety.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sheng Yang, Doctor; Phone Number: 010-87788507; Email: medart@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or Female aged ≥18 years old;
• Histologically or cytopathologically confirmed non-small cell lung cancer (NSCLC) ;
• According to RANO-BM, the subject has at least 1 intracranial measurable lesion;
• Tumor tissue samples or blood samples are confirmed to be EGFR mutations;
• ECOG PS 0-1;
• Life expectancy >12 weeks;
• No prior systemic antitumor therapy for metastatic NSCLC

Exclusion Criteria:

• Patients without lung adenocarcinoma, including lung squamous cell carcinoma or mixed histological type, etc;
• Expected to receive other anti-tumor therapy other than the investigational product during the study;
• Having previously received systematic anti-tumor therapy
• Having received the following therapies: (1) Having been irradiated for > 30% bone marrow or a large area within 4 weeks prior to the first dose of investigational product; (2) Having received major surgery within 4 weeks prior to the first dose of investigational product or plan to receive major surgery during the study with exception of the surgical procedures to establish vascular access, biopsy through mediastinoscopy or thoracoscopy; (3) Use of a potent CYP3A4 inhibitor within 7 days prior to the first dose of investigational product or a potent CYP3A4 inducer within 21 days prior to the first dose of investigational product; use of the traditional Chinese medicine or traditional Chinese medicine preparation with tumor indication, or traditional Chinese medicine or traditional Chinese medicine preparation with adjuvant anti-tumor effect within two weeks prior to the first dose of investigational product or expected to be required during the study; (4) Having participated in the clinical trial and received the investigational product or device within 4 weeks or at least 5 half-lives prior to the first dose of investigational product; (5) Having received other anti-tumor drugs within 14 days prior to the first dose of investigational product;
• Having a history of other malignant tumor, or other concurrent malignant tumors;
• The toxicity caused by previous anti-tumor therapy has not recovered to <= CTCAE grade 1 (CTCAE 5.0) (except alopecia, sequelae of previous platinum-related neurotoxicity) ;
• Previous interstitial lung disease (ILD), drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy; or having the clinical manifestations of suspected interstitial lung disease;
• Serious gastrointestinal dysfunction, or disease that may affect the intake, transportation or absorption of investigational product;
• Recently active digestive disease
• The patient is prone to bleeding or has active bleeding; Any bleeding event ≥CTCAE grade 3 within 28 days prior to the first study drug;
• Clinically significant prolonged QT interval or other arrhythmia or clinical status considered by investigators that may increase the risk of prolonged QT interval; for example, QTc > 470 ms on ECG at resting state, complete left bundle branch block, degree III atrioventricular block, congenital long QT syndrome, serious hypokalemia, or current use of drugs that may lead to prolonged QT interval;
• Bone marrow reserve, liver, kidney organs and other functions are insufficient;
• There has been an active venous thrombosis event within the last 6 months;
• Known Active hepatitis B virus , hepatitis C virus (positive HCV Ab) or human immunodeficiency virus (positive HIV antibody) infection;
• Infectious disease requiring intravenous medication;
• Known history of mental disease or drug abuse, and currently having an attack or still taking drugs;
• Known or suspected allergy to Furmonertinib or other components of its preparation;
• Female subjects or female partners of male subjects who are pregnant or lactating, or plan to be pregnant during the study;
• Poor compliance, inability to comply with the study procedures, restriction or requirements;
• Other conditions that are considered by investigators as unsuitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furmonertinib combine with anlotinib; Furmonertinib 80mg, once daily, orally Anlotinib 12mg, once daily (days 1-14, 21 days per cycle), orally	Drug: Furmonertinib; Furmonertinib 80mg, once daily, orally; Other Names: AST2818; Drug: Anlotinib; Anlotinib 12mg, once daily (days 1-14, 21 days per cycle), orally; Other Names: No other intervention names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Nervous System Objective Response Rate (CNS ORR)	Proportion of subjects whose CNS tumors are assessed as complete response(CR) or partial response(PR) according to RANO-BM.	Approximately 12 weeks after the last patient begin study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of subjects whose tumors are assessed as complete response(CR) or partial response(PR) according to RECIST 1.1.	Approximately 12 weeks after the last patient begin study treatment
Disease Control Rate (DCR)	Proportion of subjects whose tumors are assessed as CR, PR or stable disease (SD) according to RECIST 1.1.	Approximately 12 weeks after the last patient begin study treatment
Progression Free Survival (PFS)	The time from the first dose of the study drugs to the progression of the disease or death for any reason according to RECIST 1.1	Approximately 18 months after the first patient begin study treatment
Overall survival (OS)	The time from the first dose of the study drugs to the death for any reason according to RECIST 1.1	Approximately 24 months after the last patient begin study treatment
Central Nervous System Disease Control Rate (CNS DCR)	Proportion of subjects whose CNS tumors are assessed as CR, PR or stable disease (SD) according to RANO-BM.	Approximately 12 weeks after the last patient begin study treatment
Central Nervous System Progression Free Survival (PFS)	The time from the first dose of the study drugs to the progression of the CNS disease or death for any reason according to RECIST 1.1	Approximately 18 months after the first patient begin study treatment
Adverse Events (AEs)	The number of patients with adverse events and the severity according to CTCAE v5.0	rom the start of study drug to 28 days after the last dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline and time to deterioration in gene mutation spectrum of ctDNA	Gene mutation spectrum of ctDNA will be detected by NGS. The development of resistance will be monitored.	Approximately 18 months from the last patient begin study treatment

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Sheng Yang, Doctor, Cancer hospital, CAMS

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: June 29, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 29, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: EGFR mutation; Brain metastasis; Adenocarcinoma of Lung
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Adenocarcinoma; Brain Neoplasms; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Aflutinib
• Other Study ID Numbers: 23/469-4212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No