The data we presented at ASCO is for the RASolute 302 clinical trial. This is a clinical trial to look at new treatments in patients with metastatic pancreatic cancer. A problem with pancreatic cancer has been that it has been very difficult to treat, we don’t have that many different therapies and the primary treatment we use is chemotherapy. So this clinical trial is using a new drug that blocks RAS because RAS mutations are seen in almost 95% of pancreatic cancers, so very, very common. We have known for years that we would like to try to inhibit this mutation as a treatment strategy and finally now some new medicines are coming that are allowing us to do that, daraxonrasib being one of those.
Could you outline the methodology?
So the RASolute 302 trial is a large randomised global study that randomised patients 1:1 to either receive daraxonrasib or to receive standard of care chemotherapy. Patients had to have metastatic pancreatic cancer to be eligible, they also needed to have received one prior line of treatment, which is chemotherapy in pancreatic cancer. They actually could have any RAS mutation, the variety of RAS mutations we see in pancreatic cancer, all those patients were eligible. In addition, we didn’t actually require that a RAS mutation was present, so it really allowed any patient with previously treated metastatic pancreatic cancer to enrol to the study.
The primary outcomes of the study were co-primary endpoints of overall survival and progression free survival. This was a global study across six countries in Asia, Europe and in North America.
What did you find?
The results for RASolute 302 showed that daraxonrasib statistically significantly improved all of the primary and key secondary endpoints. To start with, it was shown to demonstrate increased survival, a statistically significant improvement in overall survival for daraxonrasib compared to chemotherapy. The median overall survival was 13.2 months for daraxonrasib and 6.7 months for chemotherapy.
As a key next endpoint we looked at progression free survival. In that setting daraxonrasib also demonstrated a statistically significant improvement in progression free survival compared to chemotherapy. We next looked at objective response rate, again daraxonrasib demonstrated an improvement in objective response rate compared to chemotherapy. In this setting the response rate to daraxonrasib was a little over 30% and for chemotherapy approximately 11%. We then looked at quality of life and pain, which is an important symptom for patients with pancreatic cancer, and showed that daraxonrasib led to better improvements and less progression of pain and more improvement in quality of life compared to chemotherapy.
Finally, when we looked at the side effects of therapy, the main side effects of daraxonrasib were rash and mucositis, so inflammation in the mouth. The side effects from chemotherapy are what we have seen for chemotherapy for many years – blood count suppression, peripheral neuropathy, nausea, diarrhoea and those. Overall what we saw is there was less dose reductions in daraxonrasib than chemotherapy and fewer patients stopped daraxonrasib – only about 1% compared to 11% of patients who stopped chemotherapy because of side effects.
In summary, what RASolute 302 demonstrated was that daraxonrasib led to improvements in overall survival, progression free survival, objective response rate and quality of life compared to chemotherapy, with a manageable safety profile. We believe that this study has shown that daraxonrasib would be an appropriate standard of care for patients with previously treated metastatic pancreatic cancer.
