Abstract 1210P
Background
Currently neither chemotherapy nor approved EGFR TKIs have satisfactory efficacy in most EGFR 20ins mutations. Activity of furmonertinib, a novel 3rd generation EGFR TKI, against EGFR 20ins was assessed in preclinical models and a phase Ib study.
Methods
The preclinical activity of furmonertinib were evaluated in vitro and in vivo. Then the clinical efficacy and safety were investigated in a phase Ib study (FAVOUR 1, NCT04858958) in which 30 advanced NSCLC patients (pts) with EGFR 20ins were planned to be enrolled: Cohort 1 (10 pts): treatment-naïve, furmonertinib 240mg qd; cohort 2 and 3: previously treated, 240mg qd and 160mg qd respectively. Previously treated pts would be randomized into cohort 2 or 3. The primary endpoint was ORR.
Results
In preclinical studies, furmonertinib effectively inhibited BaF3 cells expressing EGFR 20ins with mean IC50 of 11∼20 nM. Good efficacy and well tolerance were also observed in patient-derived xenograft models harboring EGFR 20ins (LU0387) with furmonertinib at 45mg/kg/day. As of 30 Apr 2021, 10 EGFR 20ins advanced NSCLC pts were enrolled in cohort 1 and received furmonertinib 240mg qd. In these pts: median age, 67.5y (range 47‒69); women, 70%; ECOG 0/1, 30%/70%. Median time on treatment was 3.5 months and all pts remain on treatment. At data cutoff, all pts had ≥1 disease assessment. The best response was PR in 7 pts and SD in 3 pts. 5/7 objective responses (all PR) were confirmed, with 2 awaiting confirmation. All pts showed tumor shrinkage in target lesions (median best percent change, -43.0% [-72.3%, -3.0%]). The most common treatment emergent adverse events (TEAE, ≥20%) were diarrhea, paronychia, skin fissures (each 30%), anorexia, upper respiratory tract infection, creatinine renal clearance decreased, pain in extremity, rash, face oedema and stomatitis (each 20%). No grade ≥3 TEAE was observed. Dose interruption was reported once due to diarrhea. No dose reduction or discontinuation were observed.
Conclusions
Furmonertinib has shown encouraging anti-tumor activity in EGFR 20ins NSCLC based on the preclinical data and the preliminary results of the phase Ib study without new safety signals. Further exploration of this phase Ib study is ongoing.
Clinical trial identification
NCT04858958.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Allist Pharmaceutical Technology.
Funding
Shanghai Allist Pharmaceutical Technology.
Disclosure
All authors have declared no conflicts of interest.