Alflutinib Mesylate Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer （FLAG）

NCT03787992 | Active Not Recruiting Phase 3

• 1 other identifier: 201801215
• Study Type: interventional
• Target: 358
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the efficacy and safety of Alflutinib Mesylate versus Gefitinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Conditions

Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS) (Months)

  Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent alflutinib compared with SoC EGFR-TKI therapy as measured by PFS.

  At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression ( (approximately 12 months)

Secondary Outcomes (7)

• Overall Survival (OS)- Number of Participants With an Event

  From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)

• Progression Free Survival (PFS) evaluated by investigator

  At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months)

• Objective Response Rate (ORR)

  At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months)

• Duration of Response (DoR)

  At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months)

• Depth of Response

  At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months)

Study Arms (2)

Alflutinib Mesylate (AST2818) +placebo

EXPERIMENTAL

AST2818 (80 mg or 40 mg orally, once daily) plus placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule

Drug: Alflutinib Mesylate (AST2818) 80mg//40 mg+ placebo; Drug: Placebo Gefitinib 250 mg

Gefitinib + placebo AST2818

ACTIVE COMPARATOR

Gefitinib (250 mg orally, once daily) + placebo AST2818 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule.

Drug: Gefitinib 250 mg; Drug: Placebo AST2818 80mg//40 mg

Interventions

Alflutinib Mesylate (AST2818) 80mg//40 mg+ placebo DRUG

The initial dose of AST2818 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Alflutinib Mesylate (AST2818) +placebo

Placebo Gefitinib 250 mg DRUG

The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Alflutinib Mesylate (AST2818) +placebo

Gefitinib 250 mg DRUG

The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Gefitinib + placebo AST2818

Placebo AST2818 80mg//40 mg DRUG

The initial dose of Placebo AST2818 80 mg once daily can be reduced to Placebo AST2818 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Gefitinib + placebo AST2818

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all the following criteria to be enrolled in this study: subjects will voluntarily participate and sign a written informed consent.
• Male or female, aged at least 18 years.
• ECOG performance status of 0 to 2. Life expectancy of at least 12 weeks.
• Patients had histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma not amenable to curative surgery or radiotherapy.
• The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
• Tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
• Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if the disease has no progression during one year.
• At least one measurable lesion by CT or MRI. The measureable lesion should receive no local treatments (i.e., radiotherapy) or not used for screening biopsies (If there is only one target lesion that must be biopsied, baseline tumor evaluation is required at least 14 days after screening biopsy) and can be accurately measured at baseline with the longest diameter greater than 10 mm at baseline (if it is a lymph node, short diameter greater than 15 mm is required). If the lesions located at the regions which were previously treated are confirmed to progress, they can be chosen as lesion according to RECIST Version 1.1
• Females who have fertility potential before menopause should have a pregnancy test in the time period of 7 days prior to start of dosing, should not be breast feeding and must have a negative pregnancy test (blood test or urinalysis) prior to start of dosing; Males and females of child-bearing age must take adequate contraceptive measures within 3 months after signing the informed consent of the study to the last drug treatment.

You may not qualify if:

• Treatment with any of the following:
• Patients received other systemic anticancer therapies for advanced/metastatic non-small cell lung cancer
• Patients who have received intrapleural perfusion therapy should be admitted to the group unless the stabilization of hydrothorax is longer than 28 days
• Prior treatment with an EGFR-TKI
• Major surgery within 4 weeks of the first dose of study drug
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug and local radiotherapy or palliative radiotherapy for bone metastasis within 14 days before first drug administration
• Patients receiving medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 within 7 days before first drug administration and patients continuously taking these medications during investigating period
• Patients taking traditional Chinese medicine and preparations whose therapeutic goal is anti-tumors within 7 days before first drug administration; or continuously taking these medications during investigating period
• Patients with any factors that increase the risk of QTc prolongation or risk of Torsade ventricular tachycardia event who continuously take these medications during investigating period.
• Before the first administration, the duration of discontinuation of other clinical experimental drugs was less than 14 days
• The tissue type is mixed type, that is, patients with lung adenocarcinoma mixed with lung squamous cell carcinoma.
• Patients with spinal cord compression, asymptomatic and stable brain metastases, except for those patients who have completion of the definitive therapy and steroids at least 28 days before investigation，or patients who received local radiotherapy for brain metastasis will be allowed in when the period of stabilization of brain metastases are at no shorter than 28 days.
• Patients with other malignant tumors or have a history of other malignant tumors, except for basal cell carcinoma of the skin, carcinoma in situ of the cervix and ductal carcinoma in situ of the breast.
• Any condition affecting the drug taking, or significantly affecting the absorption or the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit, chronic gastroenteropathy, disability in swallowing, history of gastrointestinal resection or surgery, uncured recurrent diarrhea, atrophic gastritis (the age of onset is less than 60 years old), stomach diseases, crohn's disease and ulcerative colitis that require long-term use of PPI antiacid drugs without cure.
• Patients of organ insufficiency in bone marrow, liver and kidney meet the following requirements (patients should receive no blood transfusion, blood product, hematopoietic stimulating factors, and albumin two weeks before blood sampling of admission )：

Sponsors & Collaborators

• Allist Pharmaceuticals, Inc.: lead

Study Sites (1)

cancer hospital Chinese academy of medical sciences

Beijing, China

Location

Related Publications (1)

• Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, Liu J, Cao L, Cheng Y, Zhao H, Zhang S, Zang A, Cui J, Feng J, Yang N, Liu F, Jiang Y, Gu C; FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-1028. doi: 10.1016/S2213-2600(22)00168-0. Epub 2022 Jun 2.

  PMID: 35662408 DERIVED

MeSH Terms

Interventions

aflutinib; Gefitinib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 27, 2018
• Study Start: May 30, 2019
• Primary Completion: September 15, 2021
• Study Completion: March 1, 2026
• Last Updated: April 11, 2025

Record last verified: 2025-03

Locations

CN (1)