InxMed与益方生物KRAS G12C结直肠癌联合疗法结果发表于Lancet Oncology

InxMed Announces Publication in The Lancet Oncology Featuring Encouraging Antitumor Activity of Ifebemtinib in Combination with Garsorasib in Previously Treated Metastatic Colorectal Cancer (CRC) Harboring KRAS G12C Mutation
NANJING, China, Aug. 28, 2026 /PRNewswire/ -- InxMed Co., Ltd ("InxMed"), a clinical-stage biotechnology company dedicated to developing innovative therapies targeting cancer treatment resistance and metastasis, today announced that the clinical results of ifebemtinib (IN10018), a highly selective focal adhesion kinase (FAK) inhibitor, in combination with garsorasib (D-1553), a potent KRAS G12C inhibitor, in previously treated KRAS G12C-mutant metastatic colorectal cancer (CRC), have been published online in The Lancet Oncology.
The data were derived from a phase Ib/II trial (NCT06166836/NCT05379946) evaluating the efficacy and safety of ifebemtinib plus garsorasib in KRAS G12C-mutant solid tumors, where ifebemtinib plus garsorasib, as an all-oral, chemotherapy-free regimen, demonstrated encouraging antitumor activity in patients with previously treated KRAS G12C-mutant metastatic CRC. This is the first clinical study, to our knowledge, to evaluate the efficacy and safety of FAK inhibitors in combination with KRAS G12C inhibitors in KRAS G12C-mutant solid tumors.
Encouraging Antitumor Efficacy and Manageable Safety Profile
The CRC cohort of this trial contains two parts: Part 1-single-arm study and Part 2-randomized study. In Part 1-single-arm study, 15 previously-treated KRAS G12C-mutant metastatic CRC patients were enrolled and received ifebemtinib (100mg once a day) plus garsorasib (600mg twice a day) orally. And in Part 2-randomized study, 36 previously-treated KRAS G12C-mutant metastatic CRC patients were enrolled and randomly assigned (1:1) to receive ifebemtinib plus garsorasib or garsorasib alone (600mg twice a day) orally. By the data cutoff on June 30, 2025, the median follow-up was 23.8 months in the single-arm study, and in the randomized study the median follow-up was 10•3 months for the combination group and 10•9 months for the monotherapy group. Key findings published in this paper were summarized below:
Objective Response Rate (ORR): In the single-arm study, 15 patients were enrolled with 14 patients evaluable, and the confirmed ORR was 46.7% (95% CI: 21.3–73.4) in the full population and 50.0% (95% CI: 23.0–77.0) in the evaluable population. In the randomized study, the confirmed ORR was 38.9% (95% CI: 17.3–64.3) in the ifebemtinib plus garsorasib group versus 16.7% (95% CI: 3.6–41.4) in the garsorasib monotherapy group, representing an absolute improvement of 22.2% in the combination group.
Progression-Free Survival (PFS): In the single-arm study, the median PFS was 6.9 months (95% CI: 2.8–12.0). In the randomized study, ifebemtinib plus garsorasib achieved a median PFS of 7.7 months (95% CI: 3.0–NE) versus 4.0 months (95% CI: 2.0–5.6) with garsorasib monotherapy group (HR 0.48, 95% CI: 0.22–1.04), pointing to a favorable PFS trend in favor of the combination.
Overall Survival (OS): In the single-arm study, the median OS was 14.3 months (95% CI: 4.7–NE). In the randomized study, the median OS was not estimable (95% CI: 10.2–NE) in ifebemtinib plus garsorasib group versus 7.5 months (95% CI: 5.3–NE) in garsorasib monotherapy group (HR 0.34, 95% CI: 0.11–1.12), suggesting a favorable OS trend in the combination group.
Manageable safety profile: Across all 33 patients receiving ifebemtinib plus garsorasib, 32 patients (97%) reported treatment-related adverse events (TRAE) with most of them reported as grade 1-2 and grade 3 TRAEs reported in 30% of patients. No grade 4 TRAEs, treatment-related deaths or TRAEs leading to study drug discontinuation were reported across all cohorts. The most common TRAEs occurring in all 33 patients receiving ifebemtinib plus garsorasib were diarrhoea, proteinuria, and nausea.
Overcoming Resistance by FAK Inhibition When Targeting KRAS
KRAS G12C mutations occur in approximately 3–4% of patients with metastatic colorectal cancer. Currently, KRAS G12C inhibitor monotherapy shows limited efficacy in this patient population, and two KRAS G12C inhibitors plus anti-EGFR antibody regimens demonstrated synergistic activity and have been approved by FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. However, anti-EGFR antibody requires intravenous administration and are commonly associated with dermatological toxicities. How to further enhance the efficacy of KRAS G12C-targeted therapy while providing a more convenient and tolerable treatment option has become a clinical imperative.
InxMed's translational research found out that KRAS G12C 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. The clinical data reported herein provide further support for ifebemtinib in combination with KRAS G12C inhibitors in the treatment of previously treated KRAS G12C-mutant metastatic CRC.
Advancing the Clinical Development
The study demonstrates that the dual-oral, chemotherapy-free regimen of ifebemtinib plus garsorasib has shown encouraging antitumor activity and a manageable safety profile in patients with previously treated KRAS G12C-mutant metastatic CRC. These findings warrant a pivotal trial of this combination regimen to further establish its clinical benefit. The company has submitted an IND application in China, for a phase III trial evaluating the efficacy and safety of ifebemtinib plus garsorasib versus investigators' choice of standard therapy for treatment of previously treated metastatic colorectal cancer harboring KRAS G12C mutation.
Based on a robust translational medicine foundation and compelling clinical evidence, Ifebemtinib is poised to become a revolutionary therapeutic that could fundamentally reshape the RAS-targeted treatment paradigm. 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 inhibitors, but also with KRAS G12D inhibitors and multi-RAS inhibitors, among other novel classes, underscoring the company's commitment to transforming the future of RAS-addicted cancers.
About Ifebemtinib (IN10018)
Ifebemtinib (IN10018) is an orally available, highly potent, and selective small-molecule inhibitor of focal adhesion kinase (FAK). InxMed holds exclusive global development and commercialization rights. Clinically, ifebemtinib has demonstrated excellent safety and tolerability in over 700 subjects globally, showing vast 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.
About InxMed
Founded in 2017, InxMed is a late clinical-stage biotechnology company dedicated to tackling a central challenge in cancer therapy—drug resistance caused by tumor defense mechanisms. Our strategy focuses on critical signaling hubs shared across multiple tumor types, most notably the focal adhesion kinase (FAK) and integrin pathways, which play pivotal roles in tumor cell survival and contribute to treatment failure across various therapeutic modalities. In parallel, we target cancer-associated fibroblasts (CAFs) to dismantle the protective barrier around tumor cells. Through these integrated efforts, we aim to redefine cancer treatment and pioneer new frontiers in therapeutic innovation. For more information, please visit en.inxmed.com.
SOURCE InxMed Co., Ltd