Non-Small-Cell Lung Cancer
Conditions
Keywords
EGFR mutations; furmonertinib; anlotinib; non-squamous NSCLC
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.
Interventions
DRUGFurmonertinib
80mg/day orally on a continuous dosing schedule. If subjects suffer from AEs, they can get declined dosage (40mg).
DRUGAnlotinib
10mg/day orally from day 1 to 14 of a 21-day cycle. If subjects suffer from AEs, they can get declined dosage (8mg).
Sponsors
Allist Pharmaceuticals, Inc.
Shanghai Chest Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Approximately 3 years following the first dose of study drugs | Proportion of subjects whose tumors were assessed as complete response(CR) or partial response(PR) according to RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Approximately 3 years following the first dose of study drugs | Proportion of subjects whose tumors were assessed as CR, PR or stable disease (SD) according to RECIST 1.1. |
| Duration of Response (DOR) | Approximately 3 years following the first dose of study drugs | The time from objective tumor remission (CR or PR) to the progression of the disease or death for any reason. |
| Disease progression free survival (PFS) | Approximately 3 years following the first dose of study drugs | The time from the first does of the study drugs to the progression of the disease or death for any reason. |
| Adverse Events | Until 30 days from the last dose of study drugs or initiation of a new anticancer treatment | Number of participants with adverse events as a measure of safety and tolerability. |
Countries
China
Contacts
Primary ContactBaohui Han, MD
Outcome results
None listed