Kidney cancers frequently have mutations in the von Hippel-Lindau (VHL) gene, resulting in high levels of a protein called hypoxia-inducible factor, or HIF-2α. This results in several changes in the cancer cells and their surrounding environment that favour tumour growth. The novel hypoxia-inducible factor 2α (HIF-2α) inhibitor, belzutifan (MK-6482), blocks the action of HIF-2α.

This mini oral presentation updated the results from an ongoing small phase 2 study, where the safety and efficacy of belzutifan in combination with cabozantinib was assessed in clear cell RCC patients who had been previously treated with immunotherapy (cohort 2). (Cohort 1 included patients who were previously untreated). Just over half of the patients (54%) had been treated with one line of immunotherapy, while the remainder (46%) had previously received 2 lines of immunotherapy.

Overall, there were 52 patients in cohort 2, and the average time to when the data for this interim analysis was taken was 9 months. Most patients (88%) had tumour shrinkage. Cancer shrinkage (overall response rate) was 22%, which included 9 partial responses. 90% of patients had a complete response, partial response, or stable disease. Progression-free survival was 16.8 months and 81% of patients survived at least one year. The study is still ongoing.

Nearly all patients (98%) had a treatment-related side effect, although most (92%) were mild or moderate. The most common severe side effects were: High blood pressure (hypertension), low blood iron levels (anaemia), and feeling tired (fatigue). There were no life-threatening side effects or deaths related to treatment. Only 6 patients (12%) stopped treatment due to side effects from belzutifan and 8 patients (15%) stopped treatment due to side effects from cabozantinib.

In conclusion, belzutifan (MK-6482) showed promising anti-cancer activity when given with cabozantinib in patients with metastatic clear cell RCC that had been previously treated. There is not a lot of follow up information from the patients in this study and we will see whether these results continue to improve with time. The big question is whether this combination is a better option than the use of belzutifan alone.

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