The study at AACR was about the combination of a new RAS inhibitor and chemotherapy in patients with pancreatic cancer, particularly patients who had metastatic pancreatic cancer and no prior treatment before.

What was the study design?

This was a study to identify the dose of a RAS inhibitor known as daraxonrasib plus chemotherapy which, in this instance, was gemcitabine and nab-paclitaxel. So the study design had an initial component that looked at different doses and schedules of these drugs and then had an expansion component that treated an additional cohort of patients at the defined dose.

What were the results of this study?

The results of the study demonstrated that you could add daraxonrasib, which is a RAS inhibitor, to chemotherapy with tolerable safety for patients, meaning the side effect profile was tolerable for patients. It also demonstrated promising activity in these patients. The total cohort was 40 patients, so still relatively small, but the data so far had suggested that there was a high response rate, so the objective response rate was 58% to this combination. Also some durability to that as about 84% of patients still had been on therapy without progression of their cancer at six months.

What is the importance of these results?

Pancreatic cancer has been difficult to treat. Right now most patients get chemotherapy and the chemotherapy does have side effects and doesn’t last, meaning the response of the tumour doesn’t last as long as we would like. Over 90% of pancreatic cancers have a mutation in KRAS, so for many years we have wanted drugs that could block mutant RAS as that’s a known driver of pancreatic cancer.

Finally, after a lot of work by many people there are some of these RAS inhibitors that are now coming to clinic. Daraxonrasib, which was tested in this study, is one of them. The importance is that the study suggests adding a RAS inhibitor to chemotherapy may improve upon the efficacy of the treatment we use in patients with pancreatic cancer. That has now led to a large phase III clinical trial which is open and enrolling patients to test this combination – a RAS inhibitor plus chemotherapy – in patients with newly diagnosed metastatic pancreatic cancer.