Furmonertinib is a highly brain-penetrant, pan epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with activity against EGFR classical, T790M resistant and Ex20ins mutations. Icotinib is a first-generation EGFR TKI widely used in China and may overcome the resistance of furmonertinib due to EGFR C797S mutation. Furmonertinib plus icotinib may delay emergence of acquired resistance in the first-line setting.
This ongoing phase II study enrolled untreated advanced non-small cell lung cancer (NSCLC) patients with Ex19Del/L858R/Ex20ins mutation. Patients with stable central nervous system (CNS) metastases were allowed to enroll. The regimen consisted of furmonertinib (80 mg p.o, qd) and icotinib (125 mg p.o, tid). The primary endpoint was PFS. Secondary endpoints were ORR, DCR, OS, and safety.
40 patients were planned to be enrolled in this study. As of Nov 30 2022, 18 patients were enrolled and received study treatment. Patients’ baseline characteristics included median age 61.5-years (range 43–82), female 55.6%, ECOG PS 0/1/2 0/88.9%/11.1%, Ex19Del/L858R/Ex20ins 55.6%/38.9%/5.6%, CNS metastases 83.3%. Median follow-up was 230 days and the median PFS was not yet reached. The confirmed ORR assessed by investigator based on RECIST 1.1 was 88.9% (16 PR), DCR was 100% (16 PR, 2 SD). In patients with CNS metastasis the ORR was 86.7%, and the DCR was 100%. Tumor shrinkage was observed in all patients with a median best percent change of −34.3% (range: −76.1, −27.1). The most commonly observed treatment-emergent adverse events (TEAEs) included diarrhea, liver enzyme elevation and rash. One patient experienced a grade 3 TEAE due to diarrhea, and no other grade≥3 TEAE was observed.
Furmonertinib plus icotinib as first-line treatment showed encouraging antitumor activity and well tolerated safety profile in EGFR-mutated NSCLC. The observed AEs were consistent with those previously reported. This study is still ongoing and more results will be evaluated in the future, which may contribute to definite the role of dual EGFR TKI therapy in first-line setting.
ChiCTR2200060151.
The authors.
Shanghai Allist Pharmaceuticals Co., Ltd, Shanghai, China.
All authors have declared no conflicts of interest.