NCT06652048
Recruiting
Phase 2
High-dose Furmonertinib or Combined With Pemetrexed and Carboplatin/Cisplatin in EGFR-sensitive Mutation Advanced NSCLC After Disease Progression on First-line Treatment of Third-generation EGFR-TKI:a Multicencer,Open-label,Randomized Phase II Study
Jialei Wang1 site in 1 country60 target enrollmentStarted: October 1, 2024Last updated:
ConditionsNon-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Jialei Wang
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
Arms & Interventions
Furmonertinib 160mg QD
Experimental
All patients enrolled into this group will receive furmonertinib 160mg p.o qd.
Intervention: Furmonertinib 160mg QD (Drug)
Furmonertinib 240mg QD
Experimental
All patients enrolled into this group will receive furmonertinib 240mg p.o qd.
Intervention: Furmonertinib 240mg QD (Drug)
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]
Intervention: Furmonertinib 160mg QD plus Chemotherapy (Drug)
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: Up to 2 years
Progression-free survival (PFS) assessed by INV per RECIST v1.1 in the FAS population.
Secondary Outcomes
- 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)
Investigators
Jialei Wang
Chief physician
Fudan University
Study Sites (1)
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