ASCO GU 2020: Randomised clinical trial of HIF-2α inhibitor in patients with advanced kidney cancer

A randomised clinical trial of hypoxia inducible factor 2α (HIF-2α) inhibitor, MK-6482, was announced at the American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium in San Francisco last weekend. HIF-2α is known to stimulate the growth of tumours via the von Hippel-Lindau (VLH) group of genes. MK-6482 (also known as PT2977) blocks the action of HIF-2α and can potentially be used to slow or stop the growth of kidney cancer tumours.

In the first-in-human dose expansion study, a total of 55 patients with advanced RCC and who were not responding to treatment were given the HIF-2α inhibitor, MK-6482. The majority of patients (62%) had already received 3 or more prior drug treatments for their RCC, representing a very heavily pretreated population with limited treatment options.

The effectiveness of MK-6482 in this heavily pretreated population was encouraging, with an objective response rate of 24% (all partial responses). 56% of patients achieved stable disease, and 69% had tumour shrinkage. Only 16% of patients experienced progression of RCC. The toxicity profile compares very favourably to that of cabozantanib or everolimus plus lenvatinib.

This result is promising enough that MK-6482 is being studied in a randomised trial compared against another drug used for kidney cancer; everolimus. If this bigger study is positive, MK-6482 could be a new treatment option for advanced kidney cancer patients who have tried other drug treatments but not been successful. As it seems to be well tolerated, it might also be able to be combined with other treatments like immunotherapy in the future.

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