Eine offene, randomisierte Phase-III-Studie mit MK-6482 versus Everolimus bei Teilnehmern mit fortgeschrittenem Nierenzellkarzinom, das nach vorherigen, auf PD-1/L1- und VEGF-gezielten Therapien eine Tumorprogression aufweist (HIF-005) – AUO-Nr. AN 51/19

After failure of multiple therapeutic approaches in locally advanced or metastatic clear cell renal cell carcinoma, there is currently no evidence-based treatment option; everolimus is frequently used in this situation. MK-6482, a small molecule inhibitor of HIF-2α, is a drug that may offer an additional treatment option. HIF-2α is thought to play a role in the tumorigenesis and progression of renal cell carcinoma. MK-6482 selectively interrupts the interaction between HIF-2α and HIF-1B and could therefore be of interest as a late-line therapy. This study is being conducted to evaluate the efficacy and safety of the drug. A 1:1 randomization will be performed, stratified according to IMDC prognostic factors (0 vs. 1–2 vs. 3–6) and the number of prior VEGF/VEGF-R therapies (1 vs. 2–3). Participants in the study will receive 120 mg of MK-6482 orally once daily in Arm A, while those in Arm B will receive 10 mg of everolimus orally once daily. Treatment will continue until radiological progression according to RECIST 1.1 or the occurrence of intolerable adverse events. The primary endpoint of the study is progression-free survival (PFS) according to RECIST 1.1, assessed by an independent review board (BICR), and overall survival (OS). Secondary endpoints include response (CR or PR), time to response (DOR), assessment of treatment safety and tolerability, time to deterioration in quality of life (TTD), and characterization of health benefits as measured by the EQ-5D-5L questionnaire. This international study aims to enroll 736 patients. Eight centers in Germany are participating in the study. For patient referrals, please contact a nearby center directly (contact details in [Table 1]). [Table 2] contains a selection of the inclusion and exclusion criteria used to determine the general suitability of patients for study enrollment. The Principal Investigator (PIO) in Germany is PD Dr. M. De Santis. Her responsibilities include the medical conduct of the study, the benefit-risk assessment, and the implementation of the study protocol in Germany. She is the contact person for the ethics committee and regulatory authorities and is jointly responsible for the final medical evaluation of the results. The study sponsor is MSD Sharp & Dohme GmbH, Munich. The study is registered at clinicaltrials.gov under number NCT04195750.