High-dose Furmonertinib in the Treatment in Patients With Advanced, Metastatic NSCLC With Progressed After First- or Second-line Treatment With Osimertinib

A Prospective, Randomized, Phase ll Clinical Trial of Single-agent Treatment With Different Doses of Sulfamethoxazole Furmonertinib in Patients With Advanced, Metastatic Lung Adenocarcinoma Who Have Progressed After First- or Second-line Treatment With EGFR-TKl Osimertinib

This is a prospective, randomised, uncontrolled phase II clinical trial planned to include 84 subjects with metastatic lung adenocarcinoma that had progressed after first- or second-line treatment with Osmertinib, who were randomly assigned to trial group 1 and trial group 2, and were given Furmonertinib 160 mg and 240 mg once/day, orally, respectively, with efficacy evaluated every 6 weeks until disease progression, intolerable toxic side effects, or Subjects voluntarily withdrew informed consent.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Furmonertinib

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital
    • Contact: Yuchao Dong; Phone Number: 021-31166666; Email: dongyc1020@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic lung adenocarcinoma
• Progression of imaging-confirmed extracranial lesions after first- or second-line treatment with Osimertinib
• Previous genetic testing for a definite EGFR-sensitive mutation and imaging-confirmed extracranial lesion progression after first-line treatment with Osimertinib; or previous genetic testing for a definite T790M mutation and imaging-confirmed extracranial lesion progression after second-line treatment with Osimertinib.
• Pre-existing clinical benefit after treatment with Osimertinib, including CR, PR, SD (duration >6 months);
• Patients with at least 1 measurable lesion according to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1)
• Normal functioning of major organs
• Pre-menopausal women of childbearing potential with a negative serum or urine pregnancy test within 7 days prior to the first dose of the drug
• Subjects volunteered and signed a written informed consent form.

Exclusion Criteria:

• Previous chemotherapy or immunotherapy
• Patients with non-lung adenocarcinoma, including squamous lung cancer or mixed histological types
• Progression of imaging-confirmed extracranial lesions after prior Osimertinib treatment with accessible treatment options after genetic testing
• Patients with symptomatic brain metastases, meningeal metastases or spinal cord compression
• Any unrecovered CTCAE > grade 1 toxicity reaction following prior Osimertinib treatment at the start of study drug therapy
• Other malignant tumors within 5 years or history of other malignant tumours; except effectively controlled basal cell carcinoma of the skin, carcinoma in situ of the uterine cervix, ductal carcinoma in situ of the breast, papillary carcinoma of the thyroid, superficial bladder tumors, etc.
• History of interstitial pneumonia with previous diagnosis
• Other circumstances that, in the judgement of the investigator, make them unsuitable for inclusion in the study

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: Group A: Furmonertinib 160mg QD; Furmonertinib (AST2818) 160mg QD. All patients enrolled into this group will receive furmonertinib 160mg daily.	Drug: Furmonertinib; Drug: Furmonertinib; Other Names: AST2818
Experimental: Group B: Furmonertinib 240mg QD; Furmonertinib (AST2818) 240mg QD. All patients enrolled into this group will receive furmonertinib 240mg daily.	Drug: Furmonertinib; Drug: Furmonertinib; Other Names: AST2818

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	Objective Response Rate (ORR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments) is defined as the number (%) of patients with response	Analysis will occur when PFS maturity is observed at approximately 12 months from the first patient begin study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival (PFS) is defined as the time from beginning of study treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment.	The primary analysis of Progression-free survival (PFS) based on investigator assessment will occur when PFS maturity is observed at approximately 12 months after the first patient begin study treatment
Disease Control Rate (DCR)	Disease control rate (DCR) is defined as the percentage of subjects who have a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the Investigator.	Analysis will occur when PFS maturity is observed at approximately 12 months from the first patient begin study treatment
Duration of Response (DoR)	Duration of Response is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.	Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 12 months from the first patient begin study treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number of patients with adverse events and the severity according to CTCAE v5.0.	From the start of study drug to 30 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Shanghai Chest Hospital; Shanghai Changzheng Hospital; First Affiliated Hospital Bengbu Medical College; Fujian Provincial Hospital; The First People's Hospital of Changzhou; The General Hospital of Eastern Theater Command; Second Affiliated Hospital of Wannan Medical College

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 27, 2024
• First Submitted That Met QC Criteria: April 27, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: furmonertinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Aflutinib
• Other Study ID Numbers: CHEC2023-155

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No