In a small phase 2 study presented at the virtual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), the novel hypoxia-inducible factor 2α (HIF-2α) inhibitor, belzutifan (MK-6482), showed promising anti-cancer activity in combination with cabozantinib in patients with metastatic clear cell renal cell carcinoma (RCC) that had been previously treated.

Kidney cancers develop extra blood vessels for the delivery of oxygen and nutrients to enable the cancer to grow. A substance called hypoxia-inducible factor, HIF-2α, which is produced by a gene that is altered in kidney cancer patients, causes the growth of new blood vessels. Belzutifan (MK-6482) blocks the action of HIF-2α to stop the development of new blood vessels by the cancer.

In this preliminary analysis, the safety and efficacy of belzutifan in combination with cabozantinib was assessed in patients who had received at least 1 dose of study treatment and had 6 or more months of follow-up. Patients had received no more than 2 previous treatments for their kidney cancer. The rate of shrinkage of the tumour (response rate) was 22%, which included 9 partial responses. Most patients (90.2%) had tumour shrinkage. Time to when the drug stopped working and the cancer started growing again (progression-free survival) was 16.8 months and 95% of patients survived at least 6 months. The study is still ongoing.

Fifty-three (53) patients were included in the safety analysis. Nearly all patients (98.1%) had a treatment-related side effect, although most were mild or moderate needing only localised treatment or no treatment at all. The most common severe side effects needing hospital treatment were: High blood pressure (hypertension), low blood iron levels (anaemia), feeling tired (fatigue), changes to liver enzymes, and low blood oxygen levels (hypoxia). There were no life-threatening side effects.

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