Furmonertinib Combined With Anlotinib as the First-line Treatment in Patients With EGFR Mutation-positive NSCLC

Study Overview
=================
Brief Summary
-----------------
The aim of this phase Ⅱ study is to evaluate the efficacy and safety of Furmonertinib combined with Anlotinib as the first-line treatment in locally advanced or metastatic non-small cell lung cancer with sensitive EGFR mutations.

Official Title
-----------------
A Multi-center, One-arm Clinical Trial of Furmonertinib Combined With Anlotinib as the First-line Treatment in Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC.

Conditions
-----------------
Non-Small-Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Furmonertinib
* Drug: Anlotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects have voluntarily participated, signed and dated informed consent; Male or female subjects aged ≥18 and ≤75 years old; Locally advanced or metastatic adenocarcinoma NSCLC confirmed by histology or cytology (according to the 8th Edition of the AJCC Staging system), not suitable for surgery or radiotherapy; ECOG score 0-1, and life expectancy no less than 12 weeks according to the investigator's assessment; The tumour harbours one of the most common EGFR mutations (19del or L858R) ; According to RECIST 1.1, subjects have at least one measurable tumor lesion at baseline, and had not received radiotherapy previously; No previous systemic anti-tumor therapy for locally advanced or metastatic NSCLC. For recurrent disease, adjuvant therapy or neoadjuvant therapy may be accepted, but recurrence occurs ≥6 months from stopping treatment; Subjects with stable clinical symptoms of pleural effusion or ascites after symptomatic treatment; For premenopausal women with fertility, the result of serum or urine pregnancy test should be negative within 7 days before the first dose. Exclusion Criteria: Not lung adenocarcinoma, including lung squamous carcinoma, or mixed histology, etc; Subjects are expected to participate in other clinical studies during this trial period; Imaging evidence showed that the tumor had invaded critical blood vessels; Subjects who receive systemic anti-tumor therapy used for locally advanced or metastatic NSCLC previously; With other malignant tumors at present or history of other malignant tumors within 5 years; Leptomeningeal metastases or central nervous system metastasis requiring emergency treatment; At the beginning of study treatment, any unresolved toxic reaction to prior treatment (e.g., adjuvant chemotherapy) exceeds CTCAE Grade 1; History of ILD, drug-induced ILD, radiation pneumonitis which require steroid treatment, or with suspected clinical manifestations of ILD or high risk factors; Severe gastrointestinal dysfunction may affect the intake, transport or absorption of the study drugs; Recent active digestive diseases or other conditions that may cause gastrointestinal bleeding or perforation; Presence of bleeding constitution or active bleeding; any bleeding event ≥CTCAE grade 3, unhealed wounds, ulcers, or fractures occurred within 28 days prior to the first dose; Any of the following organ function criteria is met (no blood or blood product transfusions, no hematopoietic stimulating factors, no albumin or blood product transfusions within 7 days prior to examination): Absolute value of neutrophil (NE)<1.5 × 109/L, platelet (PLT) count<90 × 109/L, hemoglobin (HGB)<90 g/L; Serum total bilirubin (TBIL)>1.5 × ULN, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>2.5 × ULN (for liver metastases or Gilbert Syndrome, TBIL>3 × ULN, and AST and/or ALT>5 × ULN); Serum creatinine (SCr)>1.5 × ULN, or creatinine clearance<60ml/min. (According to the Cockcroft and Gault formula); Urinary protein ≥ ++, or 24-hour urine protein>1.0g; International normalized ratio（INR）>1.5 and activated partial thromboplastin time (APTT)>1.5 ULN; Fasting blood glucose >10mmol/L； Any of the following cardiac criteria is met： At rest, the mean corrected QT interval (QTc) by ECG > 470 msec； Seriously abnormal of heart rhythm, conduction, or morphology of resting ECG; Any factors that may increase the risk of prolonged QTc or risk of arrhythmic events; Left ventricular ejection fraction (LVEF) < 50%; Uncontrollable hypertension (systolic blood pressure≥150 mmHg and/or diastolic blood pressure≥100 mmHg); With active infection diseases, such as HBV, HCV and HIV; Known or suspected to be allergic to Furmonertinib and Anlotinib and / or other components of their preparations; Pregnancy or lactation; Subjects who are considered ineligible for the study for other reasons according to the investigator's assessment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furmonertinib Plus Anlotinib<br>Furmonertinib (80mg) plus Anlotinib (10mg) | Drug: Furmonertinib<br>* 80mg/day orally on a continuous dosing schedule. If subjects suffer from AEs, they can get declined dosage (40mg).<br>* Other names: AST2818;Drug: Anlotinib<br>* 10mg/day orally from day 1 to 14 of a 21-day cycle. If subjects suffer from AEs, they can get declined dosage (8mg).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Proportion of subjects whose tumors were assessed as complete response(CR) or partial response(PR) according to RECIST 1.1. | Approximately 3 years following the first dose of study drugs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Proportion of subjects whose tumors were assessed as CR, PR or stable disease (SD) according to RECIST 1.1. | Approximately 3 years following the first dose of study drugs | 
| Duration of Response (DOR) | The time from objective tumor remission (CR or PR) to the progression of the disease or death for any reason. | Approximately 3 years following the first dose of study drugs | 
| Disease progression free survival (PFS) | The time from the first does of the study drugs to the progression of the disease or death for any reason. | Approximately 3 years following the first dose of study drugs | 
| Adverse Events | Number of participants with adverse events as a measure of safety and tolerability. | Until 30 days from the last dose of study drugs or initiation of a new anticancer treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EGFR mutations; furmonertinib; anlotinib; non-squamous NSCLC