InxMed Publishes Ifebemtinib Combination Results in The Lancet Oncology, Submits Phase III IND for KRAS G12C-Mutated Colorectal Cancer

InxMed, a late-clinical-stage biotech company founded in 2017 and headquartered in Nanjing, China, has announced that results from a Phase Ib/II clinical trial evaluating ifebemtinib (IN10018) in combination with garsorasib (D-1533) have been published online in The Lancet Oncology on August 24, 2026. The publication in one of the world's most prestigious oncology journals marks a significant milestone for the company's dual-oral, chemotherapy-free approach to treating KRAS G12C mutation–positive metastatic colorectal cancer (CRC).

The study represents the first clinical evaluation worldwide of a focal adhesion kinase (FAK) inhibitor combined with a KRAS G12C inhibitor in metastatic CRC—a disease subset where the KRAS G12C mutation occurs in approximately 3–4% of patients and where existing monotherapy options have shown limited efficacy.

Trial Design and Patient Population

The reported data come from the CRC cohort of a Phase Ib/II study (NCT06166836/NCT05379946), which comprised two parts: a single-arm Phase II segment (Part 1) and a randomized controlled Phase II segment (Part 2). Data were cut off as of June 30, 2025.

In Part 1, 15 previously treated patients with KRAS G12C mutation–positive metastatic CRC received ifebemtinib at 100 mg once daily combined with garsorasib at 600 mg twice daily. In Part 2, 36 patients were randomized 1:1 to receive either the combination regimen or garsorasib monotherapy.

Efficacy Results

Objective Response Rate (ORR). In Part 1, 14 of 15 patients were evaluable for efficacy. The ORR was 46.7% (95% CI: 21.3–73.4) in the overall population and 50.0% (95% CI: 23.0–77.0) among evaluable patients. In Part 2, the combination arm achieved an ORR of 38.9% (95% CI: 17.3–64.3) versus 16.7% (95% CI: 3.6–41.4) for garsorasib alone—an absolute improvement of 22.2 percentage points.

Progression-Free Survival (PFS). In Part 1, the median PFS was 6.9 months (95% CI: 2.8–12.0). In Part 2, the combination arm demonstrated a median PFS of 7.7 months (95% CI: 3.0–not reached) compared with 4.0 months (95% CI: 2.0–5.6) for monotherapy, with a hazard ratio of 0.48 (95% CI: 0.22–1.04), indicating a meaningful reduction in the risk of disease progression.

Overall Survival (OS). In Part 1, the median OS was 14.3 months (95% CI: 4.7–not reached). In Part 2, the median OS had not been reached in the combination arm (95% CI: 10.2–not reached) versus 7.5 months (95% CI: 5.3–not reached) for monotherapy. The hazard ratio was 0.34 (95% CI: 0.11–1.12), showing a trend toward an overall survival benefit with the combination.

Safety Profile

Among all 33 patients who received ifebemtinib in combination with garsorasib, treatment-related adverse events (TRAEs) were predominantly Grade 1–2. Grade 3 TRAEs occurred at a rate of 30.3%. No Grade 4 TRAEs, treatment-related deaths, or TRAEs leading to permanent discontinuation were reported. The most commonly observed TRAEs included diarrhea, proteinuria, nausea, vomiting, and hypertriglyceridemia.

Addressing an Unmet Need

The U.S. Food and Drug Administration has approved two KRAS G12C inhibitor–anti-EGFR antibody combinations for this patient population: adagrasib plus cetuximab, and sotorasib plus panitumumab. While these regimens have demonstrated meaningful synergistic antitumor activity, both require intravenous administration of the anti-EGFR antibody, limiting clinical convenience. The ifebemtinib–garsorasib combination offers a fully oral, chemotherapy-free alternative that could address this unmet need.

Preclinical studies have shown that ifebemtinib, a potent and selective oral FAK inhibitor, can synergize with KRAS inhibitors through multiple mechanisms: suppressing FAK-YAP signaling pathway activation, reducing tumor stromal fibrosis, and inducing immunogenic cell death (ICD). These effects have been validated across multiple KRAS G12C mutation–positive tumor models, including patient-derived xenografts (PDX) from CRC patients.

Looking Ahead: Phase III IND Filed

InxMed has recently submitted an Investigational New Drug (IND) application for a Phase III clinical trial comparing ifebemtinib plus garsorasib against investigator's choice of standard treatment in previously treated patients with KRAS G12C mutation–positive metastatic CRC. The upcoming Phase III study is expected to provide confirmatory clinical evidence for this combination regimen.

Ifebemtinib has already received three Breakthrough Therapy Designations from China's National Medical Products Administration (NMPA) and one Fast Track Designation from the U.S. FDA. The company is advancing ifebemtinib across a broad RAS-mutation oncology program, with combinations involving KRAS G12C, KRAS G12D, and multi-RAS inhibitors either launched or in preparation.

About InxMed

InxMed Limited is a late-clinical-stage biotechnology company founded in 2017, dedicated to overcoming resistance—a core challenge in current cancer therapies. The company strategically targets critical signaling hubs shared across multiple tumor types, particularly focal adhesion kinase (FAK) and integrin pathways, which are essential for tumor cell survival. By also targeting cancer-associated fibroblasts (CAFs) to dismantle the protective barriers surrounding tumors, InxMed aims to reshape rational drug use in cancer treatment and pioneer new frontiers in therapeutic innovation.

InxMed has established partnerships with multiple multinational pharmaceutical companies and domestic biotech firms. Its core team includes former senior executives from Roche, Novartis, Merck, Schering-Plough, GlaxoSmithKline, Johnson & Johnson, and BeiGene, bringing deep experience in innovative drug research, development, clinical translation, proof-of-concept studies, and product commercialization—including the clinical development and regulatory approval of more than ten drugs in China, such as Keytruda and Gardasil.