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ESMO 2025 | Novel agents for KRAS G12D-mutant pancreatic cancer at ESMO 2025
Benedikt Westphalen, MD, Ludwig Maximilian University (LMU) Hospital Munich, Munich, Germany, provides an overview of recently assessed agents for KRAS G12D-mutant pancreatic cancer. GFH375 monotherapy was assessed in a Phase I/II trial (NCT06500676) and a promising overall survival and progression-free survival were recorded. In another Phase Ib/II trial (NCT06520488), HRS-4642 with gemcitabine and nab-paclitaxel demonstrated encouraging antitumor activity. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
I had the honor, together with Professor Lowry from Ireland, to chair the upper GI plenary session, and we saw two very interesting KRAS G12D compounds being presented there in the form of oral abstracts. One of them was a G12D inhibitor as monotherapy in pre-treated patients with pancreatic cancer, a great translational program attached as well, and what we see now consistently is that you’re ending up with overall response rates in the range of 30 to 50 percent, but then also progression-free survival between four and six months...
I had the honor, together with Professor Lowry from Ireland, to chair the upper GI plenary session, and we saw two very interesting KRAS G12D compounds being presented there in the form of oral abstracts. One of them was a G12D inhibitor as monotherapy in pre-treated patients with pancreatic cancer, a great translational program attached as well, and what we see now consistently is that you’re ending up with overall response rates in the range of 30 to 50 percent, but then also progression-free survival between four and six months. This is consistently over all of the trials that have now reported. And then, secondly, and this is important primary data, combining gemcitabine and nab-paclitaxel with a G12D inhibitor. In this setting, we now learn that the combination has some toxicity in terms of bone marrow toxicity, anemia, neutropenia, and so forth, but can safely be administered in combination. And yes, this was a Phase 2 clinical trial. We’re now looking at preliminary results, but the overall response rate, disease control rate, and progression and overall survival data look promising. We’ll need to see more patients, but as pointed out, this is now the time where we start mixing and matching and exploring these new agents in different settings.
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