Ifebemtinib plus garsorasib as first-line treatment for KRASG12C-mutated non-small-cell lung cancer in China: a multicentre, single-arm expansion cohort from a phase 1b/2 trial
Mené sur 33 patients atteints d'un cancer du poumon non à petites cellules présentant la mutation G12C au niveau du gène KRAS, cet essai de phase IB/II détermine la dose maximale tolérée de l'ifébemtinib (un inhibiteur de FAK dispensé par voie orale) en combinaison avec le garsorasib en traitement de première ligne puis évalue l'efficacité de cette combinaison du point de vue du taux de réponse objective
Background: Ifebemtinib, a potent selective oral inhibitor of FAK, has shown preclinical synergistic activity with KRASG12C inhibitors. Garsorasib is a novel KRASG12C inhibitor approved in China for patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC). This study aimed to evaluate the safety and efficacy of ifebemtinib plus garsorasib in KRASG12C-mutated solid tumours.
Methods: This multicentre study had a phase 1b component to establish the recommended phase 2 dose and a phase 2 multitumour expansion. Here, we report the results of the single-arm, Simon's two-stage cohort of first-line KRASG12C-mutated NSCLC from phase 2 expansion. The study was conducted at eight sites in China. Eligible patients were adults with pathologically confirmed locally advanced or metastatic NSCLC who were harbouring a KRASG12C mutation, were treatment-naive, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Enrolled patients received ifebemtinib (100 mg orally once a day) in combination with garsorasib (600 mg orally twice a day) in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent, initiation of new therapies, or death. The primary endpoint was objective response rate (ORR), as assessed by investigators, in all patients who received at least one dose of study treatment. The same population was included in safety analyses. This study is registered with ClinicalTrials.gov (NCT06166836 and NCT05379946) and is active but not recruiting.
Findings: Between April 21, 2023, and Dec 27, 2023, 33 first-line patients with NSCLC (two [6%] female and 31 [94%] male) were enrolled and received at least one dose of ifebemtinib plus garsorasib. As of Sept 16, 2025, median follow-up duration was 21·5 months (IQR 21·0–23·9). Confirmed ORR was 82% (27 of 33 patients; 95% CI 64·5–93·0). All 33 (100%) patients reported treatment-emergent adverse events, with 11 (33%) patients experiencing grade 3 or 4 events, of which eight (24%) were related to study drugs. The most frequent treatment-emergent adverse events of grade 3–4 were grade 3 proteinuria, diarrhoea, anaemia, hypertension, and pneumonia, each occurring in two (6%) of 33 patients. Serious adverse events occurred in nine (27%) of 33 patients, with intracranial haemorrhage and pneumonia being the only events reported in at least two patients (two [6%] each). No treatment-related deaths were reported.
Interpretation: The dual-oral chemotherapy-free regimen of ifebemtinib plus garsorasib had encouraging efficacy with a manageable safety profile as first-line treatment for KRASG12C-mutated NSCLC. A randomised phase 3 study has been initiated to further validate these findings against standard-of-care in the first-line setting (NCT07174908).
The Lancet Respiratory Medicine , résumé, 2026