Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer

Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer: a Single-center, Randomized Controlled Trial

This study targeted patients with resectable stage II-IIIA non-small cell lung cancer with EGFR mutation

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; Bevacizumab; Antineoplastic Agents; Carboplatin; EGFR; Tyrosine Kinase Inhibitor; Locally Advanced Non-Small Cell Lung Cancer; Pemetrexed
• Intervention / Treatment: Drug: Befotertinib combined Bevacizumab; Drug: Befotertinib combined platinum-based double chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Zhang; Phone Number: 02165115006; Email: zhangpeng1121@tongji.edu.cn
• Study Contact Backup: Name: Yue Liu; Email: 18831402353@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Yue Liu; Phone Number: 18831402353; Email: 18831402353@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• NSCLC patient with EGFR sensitive mutation as confirmed by needle biopsy;
• At stage II-IIIA (TNM Staging, Version 8) as identified by chest CT, PET-CT or/and EBUS;
• No systemic metastasis (confirmed by head MRI, whole body bone scan, PET-CT, liver and adrenal CT, etc.);
• With the feasibility to receive radical surgery ;
• Good lung function that could tolerate surgical treatment;
• Aged 18-75 years;
• At least one measurable tumor foci (the longest diameter measured by CT shall be > 10 mm);
• Other major organs shall function well (liver, kidney, blood system, etc.):
• ECOG PS score shall be 0-1;
• The child-bearing female must undergo pregnancy test within 7 days before starting the treatment and the result shall be negative. Reliable contraceptive measures, such as intrauterine device, contraceptive pill and condom, shall be adopted during the trial and within 30 days after completion of the trial. The child-bearing male shall use condom for contraception during the trial and within 30 days after completion of the trial;
• The patient shall sign the Informed Consent Form.

Exclusion Criteria:

• The patient has undergone any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment, etc.;
• The patient suffers from any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina pectoris, angina pectoris that starts to attack within the last 3 months, congestive heart failure [≥ Grade II specified by New York Heart Association (NYHA)], cardiac infarction (6 months before enrollment), severe arrhythmia and liver, kidney or metabolic diseases that requires drug treatment;
• The patient is a carrier of HIV;
• The patient has had or is currently suffering from interstitial lung disease;
• The patient had undergone other major systemic operations or suffered from severe trauma within 3 months before the trial;
• The patient is allergic to befotertinib or its any excipients;
• The patient is allergic to bevacizumab or its any excipients;
• The patient is allergic to platinum-based double chemotherapy or its any excipients;
• The female patient is in pregnancy or lactation period;
• There are any conditions under which the investigator considers the patient is not suitable to be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Befotertinib combined Bevacizumab	Drug: Befotertinib combined Bevacizumab; Befotertinib combined Bevacizumab
Experimental: Befotertinib combined platinum-based double chemotherapy	Drug: Befotertinib combined platinum-based double chemotherapy; Befotertinib combined platinum-based double chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR)	MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery	up to 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	It refers to the proportion of patients who have had a complete response or partial response (according to RECIST1.1) as confirmed by CT evaluation after 3 weeks in all patients who have completed the neoadjuvant therapy. Only patients with measurable lesions at baseline will be analyzed.	Up to 4 months
Progression-free survival (PFS)	It refers to the time (months) from the first administration of drug in this study to the disease progression or death (including any cause of death in the case of no progression) as recorded in CRF, regardless of whether the patient exits from the treatment or receives other anti-cancer treatment before progression.	up to 60 months
Disease-free survival (DFS)	It refers to the time (months) from radical surgery to relapse or death of a participant due to disease progression. In the case of a patient who still survives at the time of analysis, the latest evaluation date will be used for interpolation (censoring).	up to 60 months
Overall survival (OS)	It is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date.	up to 60 months
Event-free survival (EFS)	Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	Up to 60 months
R0 rate	It is defined as the rate of complete resection with no residual tumor cell in the resection margin.	up to 4 months
adverse event (AE) rate	It is defined as the frequency of adverse events from the participants enrolling to 30 days after the last drug administration or 30 days after surgery or new anti-cancer therapy, which comes first.	up to 4 months
Complete Pathological response (CPR)	CPR is defined as the proportion of participants who have achieved complete pathologic response (on routine hematoxylin and eosin staining, tumors with no viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery	Up to 4 months

Collaborators and Investigators

• Sponsor: Peng Zhang

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Bevacizumab; Chemotherapy; EGFR-TKI; Locally advanced non-small cell lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: LungMate-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No