High-dose Furmonertinib or Combined With Chemotherapy in EGFR-mutant Advanced NSCLC After Disease Progression on Third-generation EGFR-TKI

NCT06652048 | Recruiting Phase 2

• 1 other identifier: FLAME-003-AST2818
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label,randomised phase II study planned to include 60 subjects with EGFR-sensitive mutation advanced NSCLC after disease progression on first-line treatment with third-generation EGFR-TKI.Eligible patients will randomly be assigned in a 1:1:1 ratio to receive 160mg/240mg furmonertinib p.o qd or 160mg furmonertinib p.o qd plus chemotherapy\[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance\].Patients will be followed up every 2 cycles during the first half year , and every 3 cycles after the first half year.Treatment was continued until disease progression,intolerable toxic effects, investigator decision, patient withdrawal of consent, or death, whichever occurred first.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival (PFS) assessed by INV per RECIST v1.1 in the FAS population.

  Up to 2 years

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  Analysis will occur when PFS maturity is observed at approximately 12 months from the first patient begin study treatment

• Objective Response Rate(ORR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 2 years

• Overall Survival（OS）

  Up to 2 years

• Time to Subsequent Therapy (TTST)

  Up to 2 years

Study Arms (3)

Furmonertinib 160mg QD

EXPERIMENTAL

All patients enrolled into this group will receive furmonertinib 160mg p.o qd.

Drug: Furmonertinib 160mg QD

Furmonertinib 240mg QD

EXPERIMENTAL

All patients enrolled into this group will receive furmonertinib 240mg p.o qd.

Drug: Furmonertinib 240mg QD

Furmonertinib 160mg QD plus Chemotherapy

EXPERIMENTAL

All patients enrolled into this group will receive furmonertinib 160mg furmonertinib p.o qd plus chemotherapy\[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance\]

Drug: Furmonertinib 160mg QD plus Chemotherapy

Interventions

Furmonertinib 160mg QD DRUG

All patients enrolled into this group will receive furmonertinib 160mg p.o qd.

Furmonertinib 160mg QD

Furmonertinib 240mg QD DRUG

All patients enrolled into this group will receive furmonertinib 240mg p.o qd.

Furmonertinib 240mg QD

Furmonertinib 160mg QD plus Chemotherapy DRUG

All patients enrolled into this group will receive furmonertinib 160mg furmonertinib p.o qd plus chemotherapy\[(carboplatin AUC 5 / cisplatin 75mg/m2+ pemetrexed 500mg/m2) every 21 days ×4 cycles + pemetrexed 500mg/m2 every 21 days maintenance\]

Furmonertinib 160mg QD plus Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic non-small cell lung cancer ;
• Histologically or haematologically confirmed EGFR-sensitive mutations;
• Developed radiological progression after first-line third-generation EGFR-TKI monotherapy without any other subsequent systemic therapy. Patients received Osimertinib or Almonertinib for at least 3 months prior to progression and were discontinued 8 days prior to randomization, patients received Furmonertinib prior to progression achieved remission or sustained clinical benefit for at least 6 months (progression occurred during or \<6 months after the last dose when the third-generation EGFR-TKI as a neoadjuvant/adjuvant , EGFR-TKI is considered as first-line treatment); Patients who had previously received chemotherapy or immunotherapy as neoadjuvant or adjuvant therapy could be included if they had metastatic/recurrent disease diagnosed more than 6 months after the last treatment and had radiographic progression after third-generation EGFR-TKI therapy;
• Patient has at least one accurately measurable lesion that has not been previously irradiated or biopsied during the screening period, according to RECIST 1.1; If the patient has one and only one measurable lesion, tissue biopsy of the lesion is permitted if the investigator assesses has limited impact on lesion detection, but baseline imaging of the lesion should be performed after tissue biopsy;
• Age ≥18 years old;
• ECOG 0-1 and had not worsened 2 weeks prior to enrollment;
• Life expectancy ≥ 12 weeks;
• Female patients of reproductive age must have a blood pregnancy test within 7 days before the first medication and it is negative; Infertile women can avoid pregnancy tests and contraception.;
• Able to comply with study protocols;
• Patient himself voluntarily participated and signed the informed consent.

You may not qualify if:

• The tumor is confirmed by histology or cytology to be complicated with small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma component or squamous cell carcinoma component exceeding 10%;
• There are other driver gene mutations with known drug therapy (such as MET amplification, RET fusion, BRAF V600E mutation, etc.);
• Allergy to the study drug and/or its excipients is known or suspected;
• Treatment with any of the following:
• Received any systemic anti-tumor therapy other than third-generation EGFR-TKI (including anti-tumor drugs in clinical research) before the first dose, and received cytotoxic drugs with significant delayed toxicity, such as mitomycin C and nitrosoureas, within 6 weeks before the first dose;
• Received non-specific immunomodulators (including but not limited to interferon, IL-2), Chinese medicine or Chinese medicine preparations approved for anti-tumor indications within 2 weeks prior to initial administration;
• Received a potent inhibitor of cytochrome P450 3A4 enzyme (CYP3A4) or a potent inducer within 7 days prior to the initial study drug administration, or who require continued treatment with these drugs during the study period;
• Chest radiation therapy \> 30 Gy within 6 months prior to initial dosing; Non-thoracic (except central nervous system) radiation therapy of \>30 Gy within 4 weeks prior to initial dosing; Receiving palliative radiotherapy ≤30Gy within 2 weeks before the first dose;
• Received intrapleural perfusion were not admitted until 28 days or more after the pleural fluid had stabilized;
• Major surgery within 28 days of the first dose of study drug;
• 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;
• The toxicity associated with previous antitumor therapy did not return to ≤CTCAE Class 1, except for hair loss or chemotherapy-induced ≤CTCAE class 2 peripheral neurotoxicity;
• There is spinal cord compression or symptomatic central nervous system (CNS) metastasis; Patients who were asymptomatic, stable, and did not require steroid treatment for 14 days or more before the first study drug administration were excluded. Patients who had received local CNS metastasis radiotherapy could only be enrolled after the end of radiotherapy and CNS metastasis symptoms were stable for 14 days or more;
• Have other malignant tumors within the last 5 years or have a history of other malignant tumors, except skin basal cell carcinoma, cervical carcinoma in situ and breast ductal carcinoma in situ, which have been effectively controlled for more than 3 years;
• Recent active peptic diseases, such as duodenal ulcer, ulcerative colitis, ileitis, etc., intestinal perforation, intestinal fistula, or other conditions that may lead to gastrointestinal bleeding or perforation as prescribed by the investigator; Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or prior major intestinal resection, which as determined by the investigator;

Sponsors & Collaborators

• Jialei Wang: lead

Study Sites (1)

Fudan university shanghai cancer center

Shanghai, Shanghai Municipality, 021, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aflutinib; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Jialei Wang

CONTACT

18017312369; wangjialei@shca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: October 22, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

CN (1)