InxMed Co., Ltd presented compelling Phase Ib/II clinical trial data at the 2025 ASCO Annual Meeting demonstrating the efficacy of ifebemtinib (IN10018) combined with garsorasib (D-1533) in KRAS G12C-mutant solid tumors. The dual-oral, chemotherapy-free regimen showed unprecedented survival outcomes in non-small cell lung cancer and superior response rates in colorectal cancer compared to monotherapy.
Exceptional Survival Outcomes in First-Line NSCLC
The single-arm cohort enrolled 33 first-line NSCLC patients with KRAS G12C mutations, regardless of PD-L1 expression status, with a median follow-up of 16.0 months as of March 31, 2025. The combination therapy achieved remarkable efficacy metrics:
- Median progression-free survival: 22.3 months
- Median duration of response: 19.4 months
- Median overall survival: not yet reached, with survival curves showing significant uplifting and flattening patterns indicating durable benefit
- Objective response rate: 90.3% (previously reported at ESMO 2024)
The treatment demonstrated consistent efficacy across all patients regardless of PD-L1 expression status, addressing a significant unmet need in KRAS G12C-mutant NSCLC.
Randomized Trial Validates Combination Benefit in Colorectal Cancer
In the colorectal cancer cohort, 36 previously treated patients with KRAS G12C mutations were randomized 1:1 to receive either the ifebemtinib-garsorasib combination or garsorasib monotherapy. The combination arm demonstrated clear superiority across multiple endpoints:
- Objective response rate: 44.4% versus 16.7% for monotherapy
- Disease control rate: 100.0% versus 77.8% for monotherapy
- Median progression-free survival: 7.7 months versus 4.0 months for monotherapy
- Median overall survival: not yet reached in the combination arm, with early separation observed in survival curves
Mechanism and Clinical Development Strategy
Ifebemtinib is a highly selective, oral focal adhesion kinase (FAK) inhibitor that has demonstrated synergies with multiple therapeutic modalities including chemotherapy, targeted therapies, and immunotherapies. The drug has been administered to over 600 patients with a favorable safety and tolerability profile.
"These results validate ifebemtinib as an ideal combination partner for RAS inhibitors in RAS-driven malignancies to boost efficacy of RASi significantly," said Dr. Zaiqi Wang, Chief Executive Officer of InxMed. "The unprecedented 19-month DOR and 22-month median PFS in front-line NSCLC in all comers and near doubling of response rate in CRC position this dual-oral regimen as a potential paradigm shift treatment in KRAS G12C-mutant cancers."
Regulatory Progress and Future Development
Ifebemtinib has received significant regulatory recognition, including Breakthrough Therapy Designation from the China National Medical Products Administration (NMPA) and Fast-Track Designation from the U.S. Food and Drug Administration (FDA). InxMed plans to submit a New Drug Application to the NMPA in 2025.
Based on these promising results, InxMed has initiated a randomized Phase III pivotal trial in first-line KRAS G12C-mutant NSCLC. The company is also actively exploring combinations of ifebemtinib with other KRAS-targeted agents, including KRAS G12D inhibitors and multi-RAS inhibitors, supported by promising preclinical synergy data.
The clinical data were presented at the 2025 ASCO Annual Meeting under Abstract #8629 at Poster Board #109, representing results from two ongoing clinical trials (NCT06166836; NCT05379946).
