An open-label, randomized phase 3 study of MK-6482 in combination with Lenvatinib (MK-7902) versus Cabozantinib as second or third line therapy in participants with advanced renal cell carcinoma whose disease has progressed after prior anti-PD-1/L1 therapy.

Summary description of the study

Transcription factors are molecules in our cells that influence which genes are activated or not. Faultily regulated genes play an important role in tumor formation and growth. MK-6482 is a substance that inhibits a transcription factor that is often present in excessive amounts in renal cell carcinomas. By inhibiting this transcription factor, the activity of genes that promote tumor growth can also be reduced, thus counteracting tumor progression. Lenvatinib is an inhibitor of molecules that promote cell growth and the formation of new blood vessels. By inhibiting blood vessel formation, the nutrient supply to the tumor is reduced, thus counteracting tumor growth. The combination of MK-6482 and Lenvatinib thus attacks tumor progression on two different levels. Cabozantinib is an approved standard treatment for renal cell carcinoma (RCC) with a clear cell component. This study investigates the efficacy and tolerability of the combination of MK-6482 with Lenvatinib compared to Cabozantinib in patients with advanced renal cell carcinoma (RCC) with a clear cell component, whose disease has progressed during or after standard therapy with a PD-1/L-1 antibody. The study will last approximately 4 years. Participants will receive the study medication until their cancer worsens, they begin another cancer treatment, or their participation in the study ends. After discontinuation of the study medication, a follow-up phase will follow.

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Intervention under investigation

Approximately 708 patients will participate in the study worldwide, with about 18 in Switzerland.

After a thorough eligibility assessment and entry examination, as well as a preparatory discussion with the study physician, participants will receive treatment with MK-6482 and Lenvatinib or with Cabozantinib.

Treatment phase:

Study participants will be randomly assigned to two groups.

All participants in group 1 will receive one MK-6482 (120 mg) and one Lenvatinib (20 mg) tablet to swallow daily.

All participants in group 2 will receive one Cabozantinib (60 mg) tablet to swallow daily.

The study treatment will last for both groups until the disease worsens or treatment must be discontinued due to side effects. The study physician will discuss the next steps with the participant.

As part of the study visits, various measures and examinations may be conducted:

Discussions with medical staff, blood draws, blood pressure measurements, electrocardiograms (ECG), urine samples, scans with computed tomography (CT) or magnetic resonance imaging (MRI) with or without intravenously administered contrast agent, etc.

30 days after the completion of treatment or study discontinuation, a follow-up will occur before the participant enters the follow-up phase.

Follow-up phase:

If the study medication was discontinued due to disease progression or the start of a new therapy, the participant will be contacted every 12 weeks and asked about their health status.

If the medication was discontinued for reasons other than disease progression, the participant will continue to undergo imaging examinations every 8 weeks for the first 80 weeks, and then once every 12 weeks.

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Disease under investigation

This study includes patients with advanced renal cell carcinoma (RCC) with a clear cell component, whose disease has progressed after anti-PD-1/L1 therapy. All participants have undergone one or more unsuccessful cancer treatments prior to the study, and their cancer is often so advanced that metastases have formed. Despite improvements in the treatment of advanced renal cell carcinoma in recent years, there is still a great need for effective therapies, especially after the failure of first-line therapy. Worldwide, in 2018 there were 403,262 new cases and 175,098 deaths among renal cell carcinoma patients.

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Sponsor

MSD Merck Sharp & Dohme AG Luzern

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Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Zurich

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Date of authorisation

02.02.2021

(BASEC)

Results of the trial