Multinational first-in-human phase 1 study of the HIF-2α inhibitor DFF332 for advanced clear-cell renal cell carcinoma

Hypoxia-inducible factor (HIF)-2α is implicated in the oncogenesis of approximately 50% of patients with clear-cell renal cell carcinoma (ccRCC). A multinational first-in-human phase 1 study evaluated the HIF-2α inhibitor DFF332 for heavily pretreated advanced ccRCC. Forty patients (median age, 62.5 years) received DFF332 (25 to 150 mg once daily or 50 or 100 mg weekly) for a median duration of 12.1 weeks. Two patients (5%) achieve partial response, and 19 (47.5%) achieved stable disease as the best overall response. The safety profile was favorable, with treatment-related adverse events in 25 patients (62.5%). Only five patients I12.5%) had treatment-related anemia, and no hypoxia was observed. Serious hypertension was reported in one patient. The maximun tolerated dose was not reached. The authors conclude that further investigation is required to establish a recommended dose regimen, assess its efficacy and safety, and evaluate its full potential as a partner in combination studies.