Firmonertinib combined with platinum-based chemotherapy in patients with <i>EGFR</i> -mutant advanced NSCLC following disease progression on first-line third-generation EGFR-TKI.

Abstract

8610 Background: Patients (pts) who have progressed after first-line 3rd-generation EGFR-TKIs treatment exhibit limited therapeutic options. We report the preliminary antitumor activity and safety results of firmonertinib combined with platinum-based chemotherapy (Cohort C) in pts with EGFR-mutant advanced NSCLC who failed first-line 3rd-generation EGFR-TKIs from a prospective multi-cohort phase 2 trial (NCT06652048). Methods: Cohort C planned to include 20 pts with advanced NSCLC harboring EGFR-sensitizing mutations who progressed after first-line 3rd-generation EGFR-TKIs. Study treatment was firmonertinib (160 mg once daily) with chemotherapy (pemetrexed [500 mg/m 2 ] plus either cisplatin [75 mg/m 2 ] or carboplatin [AUC 5]). The primary endpoint was progression-free survival (PFS) assessed by investigators according to RECIST v1.1. Results: Cohort C completed accrual with 18 pts who received at least one dose of study treatment: median age was 64.5 years (range 43 to 80), ten (55.6%) were female, 16 (88.9%) were ECOG PS 1, nine (50%) were exon 21 L858R, six (33.3%) had CNS metastases at baseline. As of 30-Nov-2025, the median PFS was 8.4 months (95%CI 4.2-NR). The objective response rate (ORR) was 50.0% (95%CI 26.0-74.0). The disease control rate (DCR) was 88.9% (95%CI 65.3-98.6). The median duration of response (DOR) was not reached (95%CI 6.2-NR). The 9-month DOR rate was 75.0% (95%CI 12.8-96.1). The median overall survival (OS) was not reached (95%CI 9.1-NR). The 12-month OS rate was 70.0% (95%CI 16.2-93.3). Treatment-emergent adverse events (TEAEs) of any grade/grade≥3 occurred in 88.9%/44.4% of pts. The most common any-grade TEAEs were anemia (66.7%) and white blood cell count decreased (50%). The most common grade≥3 TEAEs were white blood cell count decreased (16.7%), neutrophil count decreased (11.1%) and anemia (11.1%). No TEAE with fatal outcome was reported. Conclusions: Firmonertinib combined with chemotherapy showed promising antitumor activity with a manageable safety profile in pts with EGFR-mutant advanced NSCLC following disease progression on first-line 3rd-generation EGFR-TKIs. Clinical trial information: NCT06652048 .