ASCO 2025 | Optimal sequencing of targeted agents in relation to IO, regorafenib, & TAS-102 for mCRC

This is such an important question as we think about what is the optimal way to bring targeted therapeutics into the clinic. I think early on we were hoping that the targeted therapeutics would stand alone and would not need chemotherapy to be active, spare the patients the toxicity of chemotherapy. But one of the things we’ve learned over the years is that there is rapid outgrowth of resistance so there probably does need to be some chemotherapy around. The other thing we’ve learned over the years looking at many targets, not just KRSG12C, but also BRAF V600E, is that it appears that chemotherapy is most active in early lines for these patients, but also the targeted therapies are most active. And when you put them together, it’s generally well tolerated and that we can increase the response rate, the durability, and importantly, the survival. So where we’re headed now is to bring these targeted therapeutics very much early on into the frontline setting together with cytotoxic chemotherapy to maximize the benefit of both of those classes together. And that appears to be leading us to better survival for these patients.

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