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This is a multicenter, open-label,randomised phase II study planned to include 60 subjects with EGFR-sensitive mutation advanced NSCLC after disease progression on first-line treatment with third-generation EGFR-TKI.Eligible patients will randomly be assigned in a 1:1:1 ratio to receive 160mg/240mg furmonertinib p.o qd or 160mg furmonertinib p.o qd plus chemotherapy[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance].Patients will be followed up every 2 cycles during the first half year , and every 3 cycles after the first half year.Treatment was continued until disease progression,intolerable toxic effects, investigator decision, patient withdrawal of consent, or death, whichever occurred first.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Furmonertinib 160mg QD | Experimental | All patients enrolled into this group will receive furmonertinib 160mg p.o qd. |
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| Furmonertinib 240mg QD | Experimental | All patients enrolled into this group will receive furmonertinib 240mg p.o qd. |
|
| Furmonertinib 160mg QD plus Chemotherapy | Experimental | All patients enrolled into this group will receive furmonertinib 160mg furmonertinib p.o qd plus chemotherapy[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance] |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Furmonertinib 160mg QD | Drug | All patients enrolled into this group will receive furmonertinib 160mg p.o qd. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | Progression-free survival (PFS) assessed by INV per RECIST v1.1 in the FAS population. | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate (DCR) | Analysis will occur when PFS maturity is observed at approximately 12 months from the first patient begin study treatment | |
| Objective Response Rate(ORR) | Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by INV based on RECIST v1.1 |
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Inclusion Criteria:
Exclusion Criteria:
The tumor is confirmed by histology or cytology to be complicated with small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma component or squamous cell carcinoma component exceeding 10%;
There are other driver gene mutations with known drug therapy (such as MET amplification, RET fusion, BRAF V600E mutation, etc.);
Allergy to the study drug and/or its excipients is known or suspected;
Treatment with any of the following:
The toxicity associated with previous antitumor therapy did not return to ≤CTCAE Class 1, except for hair loss or chemotherapy-induced ≤CTCAE class 2 peripheral neurotoxicity;
There is spinal cord compression or symptomatic central nervous system (CNS) metastasis; Patients who were asymptomatic, stable, and did not require steroid treatment for 14 days or more before the first study drug administration were excluded. Patients who had received local CNS metastasis radiotherapy could only be enrolled after the end of radiotherapy and CNS metastasis symptoms were stable for 14 days or more;
Have other malignant tumors within the last 5 years or have a history of other malignant tumors, except skin basal cell carcinoma, cervical carcinoma in situ and breast ductal carcinoma in situ, which have been effectively controlled for more than 3 years;
Recent active peptic diseases, such as duodenal ulcer, ulcerative colitis, ileitis, etc., intestinal perforation, intestinal fistula, or other conditions that may lead to gastrointestinal bleeding or perforation as prescribed by the investigator; Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or prior major intestinal resection, which as determined by the investigator;
Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension, diabetes, and active bleeding, hepatitis B (Hepatitis B surface antigen (HBsAg) positive and HBV-DNA≥500 Active infections including IU/mL or higher than the lower limit of detection), hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection), and human immunodeficiency virus (HIV) (including any patient receiving intravenous treatment for infection);
Past or current interstitial lung disease (ILD) or suspected ILD that could not be ruled out by imaging examination during screening;
Pulmonary complications resulting in clinically severe lung damage include, but are not limited to the following: Any serious underlying lung disease (e.g., pulmonary embolism diagnosed within 3 months prior to first dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, etc.) b. Any autoimmune, connective tissue, or inflammatory diseases that may involve the lungs (such as rheumatoid arthritis, Sjogren's syndrome, and sarcoidosis), and other conditions that the investigator determines may increase the risk of developing interstitial pneumonia;
Any evidence of known corneal injury;
Examination within 28 days prior to administration of the first investigational drug revealed a lack of adequate bone marrow reserve or organ function;
Any condition meets the following cardiac standard:
Patients determined by the investigator to be unable to participate in the study, such as patients with a high probability of failing to comply with the study regulations, constraints, and requirements; Or other circumstances at the discretion of the investigator;
Pregnancy or breastfeeding.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jialei Wang | Contact | 18017312369 | wangjialei@shca.org.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan university shanghai cancer center | Recruiting | Shanghai | Shanghai Municipality | 021 | China |
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| Furmonertinib 240mg QD | Drug | All patients enrolled into this group will receive furmonertinib 240mg p.o qd. |
|
| Furmonertinib 160mg QD plus Chemotherapy | Drug | All patients enrolled into this group will receive furmonertinib 160mg furmonertinib p.o qd plus chemotherapy[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance] |
|
| Up to 2 years |
| Duration of Response (DoR) | Duration of response (DoR), which is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first. | Up to 2 years |
| Overall Survival(OS) | Overall Survival (OS) in the FAS population | Up to 2 years |
| Time to Subsequent Therapy (TTST) | TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first. | Up to 2 years |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C000705711 | aflutinib |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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