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ESMO 2026 | Oral pan-RAS inhibitor GFH276 in previously treated RAS-mutated solid tumors
Yuxiang Ma, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China, discusses preliminary results from a first-in-human study (NCT07198321) of GFH276, an oral pan-RAS (ON) inhibitor, as monotherapy in heavily pretreated patients with RAS-mutated or KRAS-amplified advanced solid tumors, predominantly pancreatic cancer and non-small cell lung cancer (NSCLC). Encouraging antitumor activity was seen across multiple mutation subtypes, with ongoing trials evaluating GFH276 alone and in combination for RAS-driven malignancies. This interview took place at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid, Spain.
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Transcript
For a long time, we know that KRAS mutation is undruggable. But in recent years, we have several drugs on KRAS-G12C and G12D. And this time in ESMO, I presented another KRAS inhibitor. But it’s totally, you know, an inhibitor. The already approved drug is a K-RAS-off inhibitor, and some drugs presented in ESMO are K-RAS-on inhibitors, but it’s different. GFH-276 is a PAN-RAS, a PAN-RAS-on inhibitor of the molecular glue...
For a long time, we know that KRAS mutation is undruggable. But in recent years, we have several drugs on KRAS-G12C and G12D. And this time in ESMO, I presented another KRAS inhibitor. But it’s totally, you know, an inhibitor. The already approved drug is a K-RAS-off inhibitor, and some drugs presented in ESMO are K-RAS-on inhibitors, but it’s different. GFH-276 is a PAN-RAS, a PAN-RAS-on inhibitor of the molecular glue. It’s a new, like a different mechanism to inhibit KRAS. And this drug can, you know, focus on all the KRAS mutants, tumor models, including KRAS, NRAS, HRAS, and the different subtypes of KRAS. So yeah, the data is pretty cool. In PDAC, the pancreatic cancer, for those patients who have been treated with more than two lines of prior treatments, it can achieve 41% of the overall response rates. And for those non-solid cancer patients harboring a KRAS mutation, it also has nearly around 50% of the overall response rate. It’s quite promising for discharge.
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