Novel Agent Shows Promise in Patients with Clear Cell Renal Cell Carcinoma

A novel agent, MK-6482, demonstrated an objective response rate of 24% among patients with advanced clear cell renal cell carcinoma (RCC), according to findings from a phase 1/2 study.

“After a median follow-up of 13 months, we observed promising clinical activity in patients with heavily pretreated advanced clear cell renal cell carcinoma,” Toni Choueiri, MD, PhD, of Dana-Farber Cancer Institute, said during a presentation at the 2020 Genitourinary Cancers Symposium.

In the dose-escalation/expansion cohort trial, the researchers evaluated the oral hypoxia-inducible factor inhibitor in patients with advanced clear cell RCC treated with at least one prior line of therapy.

Safety, objective response rate, duration of response and progression-free survival (the time from treatment to disease progression or worsening) served as the trial’s primary endpoints.

The treatment led to an overall response rate of 24%, and all responses were partial responses. Partial responses occurred in two of five patients with favorable-risk disease, 10 of 40 with intermediate-risk disease, and one of 10 with poor-risk disease characteristics.

Moreover, 31 patients had stable disease as the best response to treatment. The distribution of stable disease across risk categories was similar to the distribution of objective responses. Tumor shrinkage occurred in 38 (69%) of the 55 patients.

The duration of response had yet to be reached, but the vast majority of responses persisted to six weeks and beyond. In addition, 16 (29%) patients continued treatment beyond 12 months, and 81% of responses lasted six months or longer.

Lastly, the treatment led to a median progression-free survival of 11.0 months, including a 12-month progression-free survival of 49%. Median progression-free survival ranged from 16.5 months for favorable-risk patients, to 11.0 months for the intermediate-risk group, to 6.9 months for patients with poor-risk disease characteristics.

The most common side effects were anemia (75%), fatigue (67%), dyspnea (47%), nausea (33%), cough (31%), peripheral edema (29%), vomiting (29%), headache (26%), hypoxia (26%), arthralgia (24%), dizziness (24%), diarrhea (22%), increased blood creatinine (22%), constipation (20%) and hyperkalemia (20%). The most common grade 3 side effects were anemia (26%) and hypoxia (15%).

“A phase III trial of MK-6482 is ongoing in patients with previously treated advanced clear cell renal cell carcinoma,” Choueiri said.

Investigators in the phase 3 trial of MK-6482 will enroll patients with metastatic clear cell RCC, previously treated with a PD-1/L1 inhibitor and VEGF-targeted therapy but with no more than three prior systemic therapies. The trial has an accrual target of 736 patients, who will be randomized 1:1 to single-agent MK-6842 or Afinitor everolimus). The trial has coprimary endpoints of progression-free and overall survival.