Study of Furmonertinib as Neoadjuvant Therapy for Resectable Stage Ⅱ-ⅢB EGFR Sensitive Mutant NSCLC

Sponsor

Shanghai Zhongshan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05987826

Collaborator

Xuhui Central Hospital, Shanghai (Other), Shanghai Minhang Central Hospital (Other), Shanghai Zhongshan Hospital Qingpu Branch (Other), Ningbo No. 1 Hospital (Other)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

EGFR-TKI has firmly established itself as a first-line treatment for advanced lung cancer with EGFR-sensitive mutations, and the ADAURA study has added to its indications for use as postoperative adjuvant therapy in early- and mid-stage lung cancer.However, clinical data on neoadjuvant EGFR-TKI therapy are still incomplete. A phase II clinical study, CTONG1103, currently ongoing, comparing the efficacy of the first generational EGFR-TKI erlotinib and gemcitabine combined with cisplatin as neoadjuvant therapy for stage IIIA-N2 EGFR mutation-positive non-small-cell lung cancer, did not yield significantly positive objective remission rate (ORR) results.

Furmonertinib is a third-generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets Epidermal Growth Factor Receptor (EGFR) mutations.Furmonertinib demonstrates definite efficacy and favorable safety in first-line EGFR-sensitive mutations and EGFR T790M Mutations in second-line and late-line treatment of advanced NSCLC.The aim of this study was to explore the efficacy and safety of furmonertinib neoadjuvant therapy for resectable stage II-IIIB EGFR-sensitive mutant non-small cell lung cancer efficacy and safety. Patinents are planned to be recruited from five centers in China. Eligible patients will receive furmonertinib neoadjuvant therapy for 8 weeks to evaluate the efficacy and safety of furmonnertinib neoadjuvant.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Furmonertinib	Phase 2

Detailed Description

Not Provided

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Furmonertinib Mesylate Neoadjuvant Treatment of Resectable Stage Ⅱ-ⅢB Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor（EGFR）Sensitive Mutation：a Prospective，Muliticenter，Open Label，Phase Ⅱ Single-arm Study

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Furmonertinib (AST2818) 80mg QD group All patients enrolled into this study will receive furmonertinib 80mg for 8 weeks neoadjuvant therapy before surgery.	Drug: Furmonertinib Furmonertinib 80mg QD oral 8 weeks. Other Names: Furmonertinib(AST2818)

Arm

Intervention/Treatment

Experimental: Furmonertinib (AST2818) 80mg QD group

All patients enrolled into this study will receive furmonertinib 80mg for 8 weeks neoadjuvant therapy before surgery.

Drug: Furmonertinib

Furmonertinib 80mg QD oral 8 weeks.

Other Names:

Furmonertinib(AST2818)

Outcome Measures

Primary Outcome Measures

objective response rate(ORR) [Approximately 8 weeks following the first dose of study drug]
According to RECIST 1.1 criteria, after 8 weeks of neoadjuvant therapy with furmonertinib CT scans scans assessed the proportion of patients in partial and complete remission.

Secondary Outcome Measures

Main Pathological Response（MPR） [Approximately 12 weeks following the first dose of study drug]
Proportion of resected specimens with ≤10% residual tumor cells assessed by surgical specimen pathology
Pathological Complete Response Rate（pCR) [Approximately 12 weeks following the first dose of study drug]
The proportion of patients with pathological response rate in the resected tumor.
Pathological Nodal Downstaging Rate [Approximately 12 weeks following the first dose of study drug]
Neoadjuvant confirmed by pathologic evaluation of tumors and other tissues removed during surgery Percentage of patients downregulated from lymph node-positive to negative after treatment
Delayed Surgery Rate [Approximately 12 weeks following the first dose of study drug]
Proportion of surgeries performed 2 weeks after the last dose of furmonertinib because of adverse drug reactions and other reasons.
Rate of R0 Resection [Approximately 12 weeks following the first dose of study drug]
The proportion of patients with R0 resection.
Percentage of minimally invasive mid-rotation open chest [Approximately 12 weeks following the first dose of study drug]
Proportion of minimally invasive surgeries converted to open thoracic for various reasons
Incidence of adverse drug events (AE) [Approximately 12 weeks following the first dose of study drug]
Unfavorable clinical events in the course of drug treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1）Provide informed consent prior to any study specific procedures
2）at least 18 years of age，not more than 75 years
3）Histology or cytology diagnose of non-small cell lung cancer within 60 days
4）ECOG PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks
5）Stage II-IIIB NSCLC that is expected to be resectable, as assessed by the investigator (8 thUICCTNM staging), with stage IIIB only including cT3N2M0 patients
6）According to RECIST 1.1, patients have at least one measureable tumor lesion (The longest axis ≥10mm)
7）EGFR mutation positive (exon 19 deletions or exon 21 L858R, with or without other EGFR mutations)
8）Without prior anti-tumor treatment
1. Withe adequate organ function of hematology, liver and kidney
10）Using adequate and effective contraception, Male patients should be use condoms; women should refrain from breastfeeding and have a negative pregnancy test prior to the first administration of the study drug if within during child-bearing age

Exclusion Criteria:

1）Dual or multiple primary NSCLC
2）Any prior anti-tumor treatment
3）With history of other malignancy except for radical resected tumors without recurrence for 5 years or more
4）History of interstitial lung disease or with relative risk factors
5）Diseases or clinical states with severe abnormalities of gastrointestinal function that may interfere with the ingestion, transit, or absorption of the study drug.e.g., inability to take medication orally, uncontrolled nausea and vomiting
6）Use of strong CYP3A4 inhibitors within 7 days or strong CYP3A4 inducers within 21 days before enrolment; use of traditional Chinese medicine with anti-tumor effect within 21 days before enrolment
7）With severe or uncontrolled systemic disease such as uncontrolled hypertention, diabetes mellitus, chronic heart failure, unstable angina, myocardial infarction within 1 year, active hemorrhage, active HBV/HCV/HIV or other infections requiring infusion treatment
8）Prolongation of ECG QTc or with relative risk factors
9）psychopath and/or mental illness
10）Pre-existing or coexisting bleeding disorders
11）Women with pregnancy or breastfeeding
12）Allergic to study drugs or any component
13）Other conditions that, in the opinion of the investigator, make participation in this trial inappropriate