Ifebemtinib Plus Garsorasib Shows 82% ORR and 22-Month PFS in First-Line KRAS G12C-Mutant NSCLC
核心洞察
InxMed's phase Ib/II trial of ifebemtinib plus garsorasib in first-line KRAS G12C (搜索)-mutant NSCLC reported an 82% confirmed ORR (27/33) and tumor shrinkage in all evaluable patients.
The all-oral, chemotherapy-free combination achieved a median PFS of 22.3 months and median OS of 27.8 months, with no treatment-related deaths or discontinuations.
The regimen has received Breakthrough Therapy Designation from China's NMPA and is advancing into a randomized Phase III confirmatory trial (NCT07174908).
InxMed Co., Ltd (搜索) announced that clinical results of ifebemtinib (IN10018) (搜索), a highly selective focal adhesion kinase (FAK) (搜索) inhibitor, in combination with garsorasib (D-1553) (搜索), a potent KRAS G12C (搜索) inhibitor, in first-line KRAS G12C-mutant non-small cell lung cancer (NSCLC) (搜索), have been published online in The Lancet Respiratory Medicine. The data derive from a phase Ib/II trial (NCT06166836/NCT05379946) evaluating the efficacy and safety of ifebemtinib plus garsorasib in KRAS G12C-mutant solid tumors, where the all-oral, chemotherapy-free regimen demonstrated impressive results in patients with first-line KRAS G12C-mutant NSCLC.
Promising Antitumor Efficacy and Manageable Safety Profile
A total of 33 first-line NSCLC patients with KRAS G12C (搜索) mutation were enrolled in the single-arm phase II cohort and received ifebemtinib (100 mg once daily) and garsorasib (600 mg twice daily) orally. By the data cutoff on September 16, 2025, the median follow-up duration was 21.5 months.
The combination demonstrated a high response rate and durable responses. Of the 33 enrolled patients, 31 were evaluable. The confirmed objective response rate (cORR) was 82% (27/33) across all enrolled patients and 87% (27/31) among evaluable patients. Tumor shrinkage was observed in all evaluable patients, even in the patient with a best overall response of progressive disease (PD).
Among responders, the median duration of response (DOR) was not reached (NR) (95% CI: 15.2–NE), underscoring the potential of FAK inhibition to prevent or significantly delay treatment resistance. The median progression-free survival (mPFS) reached 22.3 months (95% CI: 9.6–NE), with 12-month and 18-month PFS rates of 67.9% and 58.2%, respectively. The median overall survival (OS) was 27.8 months (95% CI: 27.8–NE), which remained immature as most patients were censored before 27.8 months. The 12-month and 24-month OS rates were 75.8% and 69.7%, respectively.
All 33 patients experienced treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2; grade 3 or 4 events occurred in 11 (33%) of 33 patients, of which eight (24%) were related to study drugs. No treatment-related deaths or treatment-related adverse events leading to drug discontinuation were reported.
"The publication of our long-term follow-up data in The Lancet Respiratory Medicine serves as a momentous validation of our translational science," said Dr. Zaiqi Wang, Chairman and Chief Executive Officer of InxMed. "By pairing KRAS G12C (搜索) inhibitor with our FAK inhibitor ifebemtinib, we have succeeded in blocking this adaptively resistant pathway. An ORR of 82% and a median PFS of over 22 months in the first-line setting represents a paradigm shift, offering these patients a highly potent, completely chemotherapy-free and all-oral option."
Overcoming Resistance by FAK Inhibition When Targeting KRAS G12C
KRAS G12C (搜索) mutations occur in roughly 12–14% of NSCLC cases. Currently, six KRAS G12C inhibitors are approved in previously-treated KRAS G12C-mutant NSCLC, including sotorasib and adagrasib (approved in the USA and Europe) and fulzerasib, garsorasib, glecirasib, and sosimerasib (approved in China). However, no KRAS G12C inhibitor monotherapy or combination regimens are approved in first-line settings, partially due to primary or acquired resistance when targeting KRAS G12C alone.
InxMed's translational research showed that KRAS G12C (搜索) inhibition alone triggers adaptive hyperactivation of the FAK-YAP signaling pathway, promotes fibrogenesis in the tumor microenvironment, and thereby enhances tumor cell survival. FAK inhibition by ifebemtinib disrupts this resistance mechanism, sensitizing tumor cells to KRAS G12C inhibition and prolonging the duration of treatment response.
Advancing the Clinical Development
Based on these promising clinical data, ifebemtinib has been granted Breakthrough Therapy Designation (BTD) in first-line NSCLC harboring KRAS G12C (搜索) mutation from the China National Medical Products Administration (NMPA). InxMed is progressing its clinical development plan, including an ongoing randomized Phase III confirmatory trial (NCT07174908) intended to support the adoption of this all-oral, chemotherapy-free regimen as a new standard of care in the front-line setting.
InxMed is strategically driving a comprehensive development program for ifebemtinib across RAS-mutant tumors, with combination regimens already initiated or in preparation not only with KRAS G12C (搜索) inhibitors, but also with KRAS G12D inhibitors and multi-RAS inhibitors, among other novel classes.
About Ifebemtinib (IN10018)
Ifebemtinib (IN10018) (搜索) is an orally available, highly potent, and selective small-molecule inhibitor of focal adhesion kinase (FAK) (搜索). InxMed holds exclusive global development and commercialization rights. Clinically, ifebemtinib has demonstrated excellent safety and tolerability in over 700 subjects globally, showing potential as a "backbone" combination partner across multiple modalities, including RAS inhibitors, immune checkpoint blockades, and antibody-drug conjugates (ADCs). It has received multiple Breakthrough Therapy Designations from the NMPA and Fast Track Designation from the U.S. FDA.