ASCO 2021 | BOREAS: KRT-232 in patients with myelofibrosis R/R to JAK inhibitors
Srdan Verstovsek, MD, The University of Texas MD Anderson Cancer Center, Houston, TX offers an update on the BOREAS study. BOREAS (NCT03662126) is a randomized, controlled, open-label, global Phase III study of KRT-232 in myelofibrosis patients who are relapsed/refractory (R/R) to Janus kinase (JAK) inhibitors. Patients will be randomized to KRT-232 or best available treatment. Primary endpoint is a spleen volume reduction (SVR) rate ≥35% at week 24. Key secondary endpoints are ≥50% reduction in total symptom score rate at week 24, progression-free survival, overall survival, best overall SVR ≥35%, and duration of spleen response. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.
Transcript (edited for clarity)
The standard practice for patients with myelofibrosis, in majority of the cases, is to implement therapy with JAK inhibitors to counteract the splenic symptoms, and perhaps try something to add to it to counter the anemia. These are the three main problems.
Now, the therapy with the JAK inhibitors is valuable, but not for too long. Unfortunately, this benefit on average appears to be lasting about three years...
The standard practice for patients with myelofibrosis, in majority of the cases, is to implement therapy with JAK inhibitors to counteract the splenic symptoms, and perhaps try something to add to it to counter the anemia. These are the three main problems.
Now, the therapy with the JAK inhibitors is valuable, but not for too long. Unfortunately, this benefit on average appears to be lasting about three years. After JAK inhibitors, after ruxolitinib, which is the usual first choice, there are not too many choices. You can try another JAK inhibitor, fedratinib. It is possible to benefit patients in controlling splenic symptoms, to some degree, a second time around. But we are looking for alternative mechanism of actions, alternative medications that would provide that optimal benefit in a second-line setting.
And here we have a medication, KRT-232, which is the MDM2 inhibitor. It’s inhibitor of this particular enzyme that is inhibitor of p53. The activity of this gene, and this result in protein, is widespread and known to allow malignancy to exist. Inhibition of inhibitor of p53 therefore would lead to very good control, at least hypothetically, of malignancy, and that’s why we have here an evidence of a good activity in a second-line setting of this particular KRT-232, good enough to talk about the Phase III randomized study for its approval. This is the BOREAS study.
The BOREAS study is a study that is based on the pilot study of KRT-232 in a second-line setting in patients that failed ruxolitinib, in which the drug had provided good control of the splenic symptoms. And now we are initiating the Phase III study where patients in a second-line setting will be randomized between the KRT-232, or best available therapy for possible approval of this drug in a second-line setting, to perhaps control the signs and signals, and prolong eventually the survival of these patients that have a short life expectancy. So, very enthusiastic approach to novel mechanism of action in the disease setting where there is not much we can do for these patients.
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