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Nat Med: Phase I trial and biomarker analysis of Belzutifan's inhibition of renal cell carcinoma

 Last Update: 2021-05-20
 Source: Internet
 Author: User

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A better understanding of the molecular biology of renal cell carcinoma (RCC) can lead to the substantial development of treatment options.

The VHL gene is lost in approximately 90% of ccRCC tumors.

Blood vessel

Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor that often accumulates in clear cell renal cell carcinoma (ccRCC), resulting in the constitutive activation of genes involved in carcinogenesis.

Belzutifan (MK-6482, formerly known as PT2977) is a potent and selective HIF-2α small molecule inhibitor.

Efficacy outcome of the ccRCC cohort

In the dose-escalation cohort (n = 43), no dose-limiting toxicity occurred and the maximum tolerated dose was not reached when the dose reached 160 mg once a day; RP2D was 120 mg once a day.

A decrease in plasma erythropoietin was observed at all doses; the concentration of erythropoietin correlated with the plasma concentration of belsutifan.

The objective response rate was 25% (all partial responses), and the median progression-free survival was 14.

Belzutifan was well tolerated and showed preliminary antitumor activity in a large number of pretreated patients.

Original source:

Toni K.

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