Robert J. Motzer, MD, on the Possible Impact of a Phase 3 Trial for Advanced ccRCC

At the American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancers Symposium, investigators announced the launch of a phase 3 trial (NCT04586231) evaluating the efficacy and safety of belzutifan (MK-6482) plus lenvatinib (Lenvima) compared with cabozantinib (Cabometyx) in patients with advanced clear cell renal cell carcinoma (ccRCC) who have progressed on prior anti–PD-1/L1 therapy.

The randomized, open-label, active-controlled, multicenter trial will include adults with histologically confirmed, unresectable, locally advanced or metastatic ccRCC with progressive disease on or after first- or second-line systemic treatment with an anti–PD-1/L1 therapy. Approximately 708 patients will be randomly assigned 1:1 to receive either MK-6482 plus lenvatinib or cabozantinib. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent.

The co-primary end points are progression-free survival per RECIST v1.1 as assessed by blinded independent central review (BICR) and overall survival. Key secondary end points include objective response rate, duration of response per RECIST v1.1 as assessed by BICR, and safety.

In an interview with CancerNetwork®, Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, explained how this regimen could potentially improve the standard of care for patients with advanced ccRCC.

Transcript:

I think it will help to define the new paradigm for people who have [immuno-oncology; IO] therapy or IO combinations in the first line. What do we do in second line? What’s the best treatment? Is it best just to go with a standard [tyrosine kinase inhibitor; TKI] or to go with this novel agent, [belzutifan], in addition to lenvatinib, which is a highly potent and effective TKI. I’m hoping it sets a new standard and results in a better outcome for patients with resistant RCC.

Reference:

Motzer RJ, Liu Y, Perini RF, Zhang Y, Heng DYC. Phase III study evaluating efficacy and safety of MK-6482 + lenvatinib versus cabozantinib for second- or third-line therapy in patients with advanced renal cell carcinoma (RCC) who progressed after prior anti-PD-1/L1 therapy. J Clin Oncol. 2021;39(suppl 6):TPS372. doi: 10.1200/JCO.2021.39.6_suppl.TPS372