Trial Title:
A Clinical Trial of Furmonertinib Combination Therapy As Neoadjuvant Treatment in Resectable EGFR-Mutated NSCLC
NCT ID:
NCT06585644
Condition:
Lung Cancer (NSCLC)
Conditions: Official terms:
Lung Neoplasms
Aflutinib
Conditions: Keywords:
Neoadjuvant
EGFR-mutant non-small-cell lung cancer
Furmonertinib
Anlotinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Furmonertinib in combination with Anrotinib and chemotherapy
Description:
The enrolled patients are planned to receive preoperative treatment with a combination of
furmonertinib and anrotinib, along with platinum-based doublet chemotherapy. Three weeks
after the completion of this treatment, they will undergo curative lung lobe resection
and systemic lymph node dissection. Postoperatively, they will continue taking
furmonertinib for one year. In case of disease progression, they will be switched to
comprehensive therapy.
Arm group label:
Treatment group
Other name:
Treatment regimen of Furmonertinib in combination with Anrotinib and chemotherapy
Summary:
Evaluate the efficacy and safety of neoadjuvant furmonertinib combined with anlotinib and
chemotherapy in patients with resectable stage II-III EGFR mutation-positive non-small
cell lung cancer.
Detailed description:
Furmonertinib is a third-generation EGFR-TKI developed by Shanghai Allist
Pharmaceuticals, capable of targeting both EGFR-sensitive mutations and the Thr790Met
mutation. The FURLONG study demonstrated that, in Chinese patients with EGFR-mutant
NSCLC, first-line treatment with furmonertinib showed superior PFS and better
tolerability compared to the first-generation EGFR-TKI gefitinib, particularly in
patients with central nervous system metastases. Anlotinib is a multi-target TKI
developed by Chia Tai Tianqing Pharmaceutical, which can inhibit multiple kinases,
including VEGFR, PDGFR, FGFR, and c-Kit, exhibiting anti-tumor angiogenesis and tumor
growth inhibition effects. The FLALTER study showed that anlotinib combined with
gefitinib significantly prolonged median PFS in treatment-naive metastatic EGFR-mutant
NSCLC patients. Preliminary results from ongoing clinical trials indicate that the ORR of
anlotinib combined with third-generation EGFR-TKIs in advanced NSCLC ranges from 65.20%
to 96.15%. Compared to adjuvant therapy, neoadjuvant therapy for resectable NSCLC offers
several potential benefits, including improved patient tolerance, early control of
microscopic metastatic disease through systemic treatment, and the potential for less
extensive surgical resection, leading to an increased rate of complete (R0) resection. So
far, the exploration of EGFR-TKIs, including gefitinib, erlotinib, and osimertinib, in
the field of neoadjuvant therapy has been undertaken. An open-label, single-arm Phase 2
study (NCT00188617) demonstrated that gefitinib is a safe and feasible option for
unselected patients with Stage I NSCLC, with an ORR of 11%. Another single-arm Phase 2
study (NCT01833572) showed that neoadjuvant gefitinib is a feasible treatment for
patients with Stage II-IIIA NSCLC harboring EGFR mutations, with an ORR of 54.5%, a MPR
rate of 24.2%, and a median DFS of 33.5 months. The EMERGING-CTONG 1103 trial was the
first randomized Phase 2 study comparing neoadjuvant erlotinib with chemotherapy in
patients with locally advanced (Stage IIIA-N2) NSCLC with EGFR-sensitive mutations. The
final results, with a median follow-up of 62.5 months, showed that the PFS in the
neoadjuvant erlotinib group was significantly longer than in the chemotherapy group,
although this did not translate into an OS benefit. Preliminary results from ongoing
clinical trials with osimertinib suggest that this third-generation EGFR-TKI is generally
safe and may be an effective neoadjuvant treatment option. This study aims to investigate
the efficacy and safety of neoadjuvant furmonertinib combined with anlotinib and
chemotherapy in resectable stage II-III EGFR-mutant NSCLC.
Criteria for eligibility:
Criteria:
Inclusion Criteria: 1) EGFR mutation-positive (including 19Del and 21L858R) non-small
cell lung cancer (NSCLC) confirmed by biopsy; 2) Resectable stage II-III NSCLC confirmed
by chest CT, PET-CT, and/or EBUS; 3) Absence of distant metastasis (including head MRI,
whole-body bone scan, PET-CT, CT of liver and adrenal glands); 4) The patient exhibits
good pulmonary function and is deemed suitable for surgical intervention; 5) Aged 18 and
above; 6)At least one measurable tumor lesion (with a longest diameter of 10mm or more as
measured by CT); 7) The ECOG score ranges from 0 to 1; 8) Women of childbearing age must
undergo a pregnancy test within 7 days prior to treatment, and the result must be
negative. During the trial period and for 30 days following its conclusion, reliable
contraceptive measures such as intrauterine devices, oral contraceptives, and condoms
should be utilized. Additionally, men of reproductive age should use condoms for
contraception during the trial period and for 30 days after its completion; 9) The other
major organs (liver, kidneys, hematological system, etc.) are functioning normally.
Hemoglobin is ≥9.0 g/dL (or can be maintained or exceeded through treatments such as
blood transfusions); the red blood cell count is ≥2.0×10^9/L; the absolute neutrophil
count is ≥1.0×10^9/L; the platelet count is ≥100×10^9/L; total bilirubin levels are
within the normal range; AST, ALT, and alkaline phosphatase levels are ≤2.5 times the
upper limit of normal; creatinine level is ≤2.0 mg/dL; creatinine clearance rate is ≥60
ml/min; patients who have not received anticoagulant therapy should have a prothrombin
time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of
normal, while patients who have undergone comprehensive or intravenous anticoagulant
therapy are eligible for clinical trials only if they have maintained stable
anticoagulant drug dosages for at least 2 weeks and their coagulation test results fall
within the target therapeutic range; 10) The patient is required to sign an informed
consent form. Exclusion Criteria: 1) The patient has undergone comprehensive anti-cancer
treatment for non-small cell lung cancer, including surgical intervention, local
radiotherapy, cytotoxic drug therapy, and targeted drug therapy; 2) The patient had no
history of any cancer other than small cell lung cancer within the 5 years prior to the
trial, with the exception of in situ cervical cancer, cured basal cell carcinoma, and
bladder epithelial neoplasms (including Ta and Tis); 3) The patient has any unstable
systemic disease (including active infection, uncontrolled hypertension, unstable angina,
recent onset of angina within the past 3 months, congestive heart failure [≥ NYHA Class
II], myocardial infarction (within the past 6 months), severe arrhythmia, and liver,
kidney or metabolic disorders requiring drug therapy); 4) The patient is a carrier of
active hepatitis B, hepatitis C, or HIV; 5) Patients with severe or newly developed
gastrointestinal diseases presenting diarrhea as the primary symptom; 6) The patient is
receiving treatment with a P-glycoprotein inhibitor; 7) Patients with a history of or
current cardiovascular malformations; 8) Patients with a history of or currently
suffering from interstitial lung disease; 9) Patients who have undergone major systemic
surgery or experienced severe trauma within the three months prior to the trial; 10)
Those afflicted with neurological disorders or psychiatric illnesses; 11) Patients
experiencing malabsorption conditions; 12) Female patients who are pregnant or lactating;
13) Other situations where researchers deem the patient unsuitable for enrollment.
Withdrawal Criteria: In the following cases, the patient will withdraw from the trial: 1)
The patient himself or his legal representative requests withdrawal; 2) The investigator
believes that the patient's continued participation in the study will be harmful to
their health; 3) The patient has developed a severe allergic reaction to the chemotherapy
drug, such as grade 3-4 exfoliative dermatitis or anaphylaxis; 4) There is any other
serious adverse reaction, and the principal investigator (PI) or a PI-designated
investigator deems it necessary to suspend treatment; 5) The patient's compliance is
very poor; 6) The patient's β-HCG test result suggests pregnancy; 7) During the study
period, the patient develops another disease. The investigator believes that the disease
will significantly affect the evaluation of the patient's clinical condition and it
is necessary to terminate the treatment plan; 8) The patient is found to have another
malignant tumor that needs to be treated; 9) The patient is lost to follow-up; 10) The
patient has taken illicit drugs or other substances judged by the investigator to be
likely to cause toxicity or lead to a bias in the study results; 11) The patient dies.
Patients who withdraw from the trial should have the reason for withdrawal documented in
both the case report form and the patient's medical record. Follow-up should be
conducted for all patients who withdraw due to adverse events or abnormal laboratory test
results, until the adverse event is resolved or stabilized, and subsequent outcomes of
the adverse events should be recorded. In cases where a patient dies during the course of
the trial or within 28 days after its conclusion, it is incumbent upon the investigator
to notify the sponsor. The cause of death must be meticulously detailed in the serious
adverse event (SAE) report form and submitted to the ethics committee within 24 hours.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Zip:
200433
Country:
China
Contact:
Last name:
Haifeng Wang, MD
Phone:
18758363835
Phone ext:
86
Email:
3891712761@qq.com
Start date:
October 1, 2024
Completion date:
June 1, 2030
Lead sponsor:
Agency:
Shanghai Pulmonary Hospital, Shanghai, China
Agency class:
Other
Source:
Shanghai Pulmonary Hospital, Shanghai, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06585644
