180 - Firmonertinib plus Radiotherapy vs. Concurrent Chemoradiotherapy followed by Firmonertinib Consolidation in Unresectable Stage III EGFR-mutant NSCLC: A Randomized Phase 2 Trial
Presenter(s)
L. Wang1, F. Ning2, L. Chen3, A. Gao1, F. Zhao1, S. Wang1, S. Wang1, Z. Yang1, X. Liao4, C. Liu1, H. Zhou1, P. Li1, C. Rao5, L. Zhao6, F. Lai7, and C. Yu8; 1Cancer Hospital of Shangdong First Medical University, Jinan, China, 2Binzhou Medical University Hospital, Binzhou, China, 3Fujian Medical University Union Hospital, Fuzhou, China, 4Chongqing University Fuling Hospital, Chongqing, China, 5Ningbo No. 2 Hospital, Ningbo, China, 6Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China, 7The First Affiliated Hospital of Fujian Medical University, Fuzhou, China, 8Huai'an First People's Hospital, Huai'an, China
Purpose/Objective(s): Definitive chemoradiotherapy (CRT) followed by consolidative osimertinib is the current standard of care for patients (pts) with unresectable (UR) stage III EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the potential of EGFR-TKI plus radiotherapy (RT) as an alternative to concurrent chemoradiotherapy (cCRT) remains undefined. Here we report the preliminary results of firmonertinib (firmo) plus RT versus cCRT followed by firmo consolidation in this population from a randomized phase 2 trial.
Materials/Methods: This randomized, multicenter, phase 2 trial enrolled pts with UR stage III EGFR-mutant NSCLC (Ex19del/L858R). Pts were randomized (1:1) to Arm A or Arm B. Arm A (Experimental): firmo (80mg QD, two 21-day cycles) with concurrent RT (60Gy). Arm B (Control): cCRT (pemetrexed 500mg/m2 + cisplatin 75mg/m2 or carboplatin AUC5 Q3W, 2 cycles) with concurrent RT (60Gy). Pts in both arms having completed concurrent RT without disease progression or grade =2 adverse events (AEs) were eligible to receive consolidative firmo until disease progression. Pts in Arm A and Arm B were each allowed to receive up to two cycles of induction treatment with firmo or chemotherapy, respectively. The primary endpoint was objective response rate (ORR) per RECIST v1.1.
Results: At the data cut-off (12 Jan 2026), a total of 36 pts had been randomized and commenced study treatment (Tx) (Arm A: 19; Arm B: 17). Baseline characteristics were balanced between arms. Overall, 78% (28/36) of pts were female (Arm A: 15; Arm B: 13). The median age was 61 years in both arms (ranges: 36–73 in Arm A and 44–75 in Arm B). The L858R mutation subtype was observed in 58% of Arm A and 65% of Arm B pts. The ORR from randomization to 42 days after RT was 68% (95%CI 43%-87%) in Arm A and 41% (95%CI 18%-67%) in Arm B. The ORR throughout the study was 74% (95%CI 49%-91%) in Arm A and 59% (95%CI 33%-82%) in Arm B. The DCR was 89% (95%CI 67%-99%) in Arm A and 82% (95%CI 57%-96%) in Arm B. The most frequently observed AEs included decreased white blood cell count, decreased neutrophil count, and radiation pneumonitis, with any-grade (grade =3) rates of 42% (5%) vs. 53% (12%), 16% (0%) vs. 41% (6%), and 26% (0%) vs. 29% (0%) in Arm A versus Arm B, respectively. No AEs led to Tx discontinuation or death.
Conclusion: In pts with UR stage III EGFR-mutant NSCLC, firmo plus RT was associated with a numerically higher ORR and a more favorable safety profile compared to standard cCRT. Long-term outcomes are under continued follow-up.