Ignite Creation Date:
2024-05-06 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 3:12 PM
Study NCT ID:
NCT06117644
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-11-07
First Post:
2023-10-31
Brief Title:
The Efficacy of Double-dose Furmonertinib in the Treatment of Patients With Slow Osimertinib-resistant NSCLC
Sponsor:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Organization:
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study Overview
Official Title:
A Single-center Prospective Study of the Efficacy of Double-dose Furmonertinib in the Treatment of Patients With Slow Osimertinib-resistant Non-small Cell Lung Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is a single-center prospective single-arm study of the efficacy of double-dose Furmonertinib in the treatment of patients with slow Osimertinib-resistant non-small cell lung cancer mainly in patients with advanced non-small cell lung cancer with EGFR-sensitive mutations in stage IIIB or IV slow drug resistance after treatment with Osimertinib and no therapeutic target was found by secondary biopsy after drug resistance
Detailed Description:
According to the latest data released by the National Cancer Center in 2022 the incidence and mortality of cancer in China are increasing year by year There are 4064 million new cancer patients in China in 2016 with a total of 2414 million cancer deaths Among them 824000 were new cases of lung cancer accounting for 204 and the number of lung cancer deaths was 657000 accounting for 272 The morbidity and mortality of lung cancer ranked first among all malignant tumors Non-small cell lung cancer NSCLC accounts for about 80 of all lung cancer types of which epidermal factor growth receptor EGFR mutation is the most common driving gene for NSCLC About 50 of Chinese patients carry this gene mutation Exon 19 deletion mutation 19Del and exon 21 L858R point mutation L858R are called classical mutations accounting for about 90 of all mutation types
With the third generation of EGFR-TKI gradually entering the clinic the survival benefits of patients with EGFR classical mutation positive NSCLC have been continuously broken through FLAURA study showed that the median progression-free survival time mPFS of Osimertinib was significantly better than that of gefitinib in the first-line treatment of advanced NSCLC patients with positive EGFR mutation 189 months VS 102 months HR 046 P 0001 In addition the third-generation domestic EGFR-TKI ametinib vometenil and so on have also been listed in China in recent years No matter in terms of survival time or quality of life the third generation of EGFR-TKI has brought clinically significant improvement to patients At present both foreign NCCN guidelines and domestic CSCO guidelines have taken the third generation of EGFR-TKI as the standard scheme for first-line treatment of EGFR classic mutation positive patients
However with the wide application of the third generation EGFR-TKI the problem of drug resistance of the third generation TKI is becoming more and more obvious The time of the third-generation TKI listing and application in China is concentrated around 2021 while the mPFS of the third-generation EGFR-TKI is concentrated between 18-22 months Therefore it can be expected that the problem of drug resistance in the third generation of TKI may continue to intensify in the next few years At present after the third generation-TKI resistance or progress there is no standard and unified treatment plan The third generation of TKI drug resistance has become a very urgent and huge clinical problem Therefore there is an urgent need to carry out clinical or real-world studies related to the third-generation TKI drug resistance to explore more or better solutions after the third-generation TKI drug resistance so as to bring more potential treatment options for the third-generation TKI drug-resistant patients
At present the exploration direction of the third generation TKI drug resistance therapy includes immune combination therapy such as Xindimazumab chemotherapy anti-angiogenic drugs precision targeted combination therapy EGFR-TKI combined with MET-TKIEGFR-TK combined with RET-TKI etc antibody coupling drugs ADC bispecific antibodies fourth generation-EGFR-TKI and so on However the above treatments may face problems such as insufficient drug accessibility excessive adverse reactions or less than expected survival time In addition to the above direction after the third-generation-TKI resistance the challenge of using the third-generation TKI with increased dose is also one of the options that may be used in clinical practice which also shows preliminary clinical value in the real world
Fumetinib methanesulfonate AST2828 is the third generation irreversible TKI At present NMPA has approved fumetinib for first-line treatment of locally advanced or metastatic NSCLC patients with positive EGFR mutation 19DelL858R and second-line posterior-line treatment for patients with disease progression with T790M mutation during or after EGFR-TKI treatment The results of its IIB phase clinical study showed that for advanced NSCLC patients with positive T790M mutation the ORR at the recommended dose of 80mg days was as high as 741 and the median PFS was 96 months The results of III phase FURLONG study showed that the mPFS of advanced EGFR mutation positive 19DelL858R NSCLC patients treated withFurmonertinib was significantly better than that of gefitinib 208months VS 111months HR044P 00001 In general the conventional dose of Furmonertinib showed a good therapeutic effect in both first-line and second-line treatment of advanced NSCLC with classical EGFR mutation
At the same time in phase I and III clinical trials some patients received daily doses of 160mg n 53 and 240mg n 18 and no dose-limiting toxicity was observed Compared with the 80mg dose group the main increases in the incidence of adverse reactions were increased alanine aminotransferase 80mg 175 1600240mg 352 decreased white blood cell count 80mg 138 1600240mg 296 decreased neutrophil count 80mg 78 1600240mg 183 increased serum creatinine 80mg 75 1600240mg 183 diarrhea 80mg 67 1600240mg 155 Anemia 80mg 60 metrology 1600240mg 239 The main increased incidence of adverse reactions in the 160-240mg dose group compared with the 80mg dose group 3 was anemia 80mg 0 meme 1600240mg 42 The results of this phase III study showed that increased doses of Furmonertinib maintained acceptable safety and tolerance
Zheng et al reported a case of successful salvage treatment with Furmonertinib 160mgd after Osimertinib resistance The clinical efficacy of oxetinib in this patient lasted only 7 months followed by sequential use of Furmonertinib160mgd After two weeks of treatment the tumor was significantly reduced and the respiratory symptoms were significantly improved At the same time the intracranial lesions of the patients were completely relieved after 1 month of treatment This case suggests that the use of increased doses of Furmonertinib may be a potential treatment option for patients with drug resistance to Osimertinib Another real-world study explored the efficacy and safety of 160mgd Furmonertinib in patients with three generations of EGFR-TKI drug resistance In 39 patients the median PFS and OS of Furmonertinib 160mgd were 47 months and 753 months respectively Among them it showed a better therapeutic effect for the third generation of TKI patients with intracranial progression with a median PFS of 545months and a median OS of 975months The main adverse reactions were anemia lymphocytopenia diarrhea and so on No new safety signal was observed This real-world study preliminarily validates the efficacy and safety of increased-doseFurmonertinib 160mgd in patients with third-generation TKI drug resistance
To sum up the researchers predict that a higher dose of 160mgd in third-generation TKI-resistant patients may have a better benefit-risk ratio which has the value of further exploration Therefore this real-world study intends to collect three generations of TKI-resistant patients who have been treated with increased doses of Furmonertinib To further analyze the efficacy and safety of improving the dose of Furmonertinib in the third generation of patients with TKI drug resistance To provide more evidence-based medical evidence for the treatment of the third generation of patients with drug resistance to TKI
With the third generation of EGFR-TKI gradually entering the clinic the survival benefits of patients with EGFR classical mutation positive NSCLC have been continuously broken through FLAURA study showed that the median progression-free survival time mPFS of Osimertinib was significantly better than that of gefitinib in the first-line treatment of advanced NSCLC patients with positive EGFR mutation 189 months VS 102 months HR 046 P 0001 In addition the third-generation domestic EGFR-TKI ametinib vometenil and so on have also been listed in China in recent years No matter in terms of survival time or quality of life the third generation of EGFR-TKI has brought clinically significant improvement to patients At present both foreign NCCN guidelines and domestic CSCO guidelines have taken the third generation of EGFR-TKI as the standard scheme for first-line treatment of EGFR classic mutation positive patients
However with the wide application of the third generation EGFR-TKI the problem of drug resistance of the third generation TKI is becoming more and more obvious The time of the third-generation TKI listing and application in China is concentrated around 2021 while the mPFS of the third-generation EGFR-TKI is concentrated between 18-22 months Therefore it can be expected that the problem of drug resistance in the third generation of TKI may continue to intensify in the next few years At present after the third generation-TKI resistance or progress there is no standard and unified treatment plan The third generation of TKI drug resistance has become a very urgent and huge clinical problem Therefore there is an urgent need to carry out clinical or real-world studies related to the third-generation TKI drug resistance to explore more or better solutions after the third-generation TKI drug resistance so as to bring more potential treatment options for the third-generation TKI drug-resistant patients
At present the exploration direction of the third generation TKI drug resistance therapy includes immune combination therapy such as Xindimazumab chemotherapy anti-angiogenic drugs precision targeted combination therapy EGFR-TKI combined with MET-TKIEGFR-TK combined with RET-TKI etc antibody coupling drugs ADC bispecific antibodies fourth generation-EGFR-TKI and so on However the above treatments may face problems such as insufficient drug accessibility excessive adverse reactions or less than expected survival time In addition to the above direction after the third-generation-TKI resistance the challenge of using the third-generation TKI with increased dose is also one of the options that may be used in clinical practice which also shows preliminary clinical value in the real world
Fumetinib methanesulfonate AST2828 is the third generation irreversible TKI At present NMPA has approved fumetinib for first-line treatment of locally advanced or metastatic NSCLC patients with positive EGFR mutation 19DelL858R and second-line posterior-line treatment for patients with disease progression with T790M mutation during or after EGFR-TKI treatment The results of its IIB phase clinical study showed that for advanced NSCLC patients with positive T790M mutation the ORR at the recommended dose of 80mg days was as high as 741 and the median PFS was 96 months The results of III phase FURLONG study showed that the mPFS of advanced EGFR mutation positive 19DelL858R NSCLC patients treated withFurmonertinib was significantly better than that of gefitinib 208months VS 111months HR044P 00001 In general the conventional dose of Furmonertinib showed a good therapeutic effect in both first-line and second-line treatment of advanced NSCLC with classical EGFR mutation
At the same time in phase I and III clinical trials some patients received daily doses of 160mg n 53 and 240mg n 18 and no dose-limiting toxicity was observed Compared with the 80mg dose group the main increases in the incidence of adverse reactions were increased alanine aminotransferase 80mg 175 1600240mg 352 decreased white blood cell count 80mg 138 1600240mg 296 decreased neutrophil count 80mg 78 1600240mg 183 increased serum creatinine 80mg 75 1600240mg 183 diarrhea 80mg 67 1600240mg 155 Anemia 80mg 60 metrology 1600240mg 239 The main increased incidence of adverse reactions in the 160-240mg dose group compared with the 80mg dose group 3 was anemia 80mg 0 meme 1600240mg 42 The results of this phase III study showed that increased doses of Furmonertinib maintained acceptable safety and tolerance
Zheng et al reported a case of successful salvage treatment with Furmonertinib 160mgd after Osimertinib resistance The clinical efficacy of oxetinib in this patient lasted only 7 months followed by sequential use of Furmonertinib160mgd After two weeks of treatment the tumor was significantly reduced and the respiratory symptoms were significantly improved At the same time the intracranial lesions of the patients were completely relieved after 1 month of treatment This case suggests that the use of increased doses of Furmonertinib may be a potential treatment option for patients with drug resistance to Osimertinib Another real-world study explored the efficacy and safety of 160mgd Furmonertinib in patients with three generations of EGFR-TKI drug resistance In 39 patients the median PFS and OS of Furmonertinib 160mgd were 47 months and 753 months respectively Among them it showed a better therapeutic effect for the third generation of TKI patients with intracranial progression with a median PFS of 545months and a median OS of 975months The main adverse reactions were anemia lymphocytopenia diarrhea and so on No new safety signal was observed This real-world study preliminarily validates the efficacy and safety of increased-doseFurmonertinib 160mgd in patients with third-generation TKI drug resistance
To sum up the researchers predict that a higher dose of 160mgd in third-generation TKI-resistant patients may have a better benefit-risk ratio which has the value of further exploration Therefore this real-world study intends to collect three generations of TKI-resistant patients who have been treated with increased doses of Furmonertinib To further analyze the efficacy and safety of improving the dose of Furmonertinib in the third generation of patients with TKI drug resistance To provide more evidence-based medical evidence for the treatment of the third generation of patients with drug resistance to TKI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None