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

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.

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.

Inclusion Criteria:

1. Subjects have voluntarily participated, signed and dated informed consent;
2. Male or female subjects aged ≥18 and ≤75 years old;
3. 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;
4. ECOG score 0-1, and life expectancy no less than 12 weeks according to the investigator's assessment;
5. The tumour harbours one of the most common EGFR mutations (19del or L858R) ;
6. According to RECIST 1.1, subjects have at least one measurable tumor lesion at baseline, and had not received radiotherapy previously;
7. 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;
8. Subjects with stable clinical symptoms of pleural effusion or ascites after symptomatic treatment;
9. 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:

1. Not lung adenocarcinoma, including lung squamous carcinoma, or mixed histology, etc;

2. Subjects are expected to participate in other clinical studies during this trial period;

3. Imaging evidence showed that the tumor had invaded critical blood vessels;

4. Subjects who receive systemic anti-tumor therapy used for locally advanced or metastatic NSCLC previously;

5. With other malignant tumors at present or history of other malignant tumors within 5 years;

6. Leptomeningeal metastases or central nervous system metastasis requiring emergency treatment;

7. At the beginning of study treatment, any unresolved toxic reaction to prior treatment (e.g., adjuvant chemotherapy) exceeds CTCAE Grade 1;

8. History of ILD, drug-induced ILD, radiation pneumonitis which require steroid treatment, or with suspected clinical manifestations of ILD or high risk factors;

9. Severe gastrointestinal dysfunction may affect the intake, transport or absorption of the study drugs;

10. Recent active digestive diseases or other conditions that may cause gastrointestinal bleeding or perforation;

11. 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;

12. 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；

13. 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);

14. With active infection diseases, such as HBV, HCV and HIV;

15. Known or suspected to be allergic to Furmonertinib and Anlotinib and / or other components of their preparations;

16. Pregnancy or lactation;

17. Subjects who are considered ineligible for the study for other reasons according to the investigator's assessment.