FDA grants breakthrough therapy designation to MK-6482 for renal cell carcinoma subtype
The FDA granted breakthrough therapy designation to MK-6482 for the treatment of certain patients with von Hippel-Lindau disease-associated renal cell carcinoma, according to a press release from the agent’s manufacturer.
MK-6482 (Merck), a novel hypoxia-inducible factor-2 (HIF-2)-alpha inhibitor, is under investigation for patients with von Hippel-Lindau disease-associated renal cell carcinoma with nonmetastatic tumors smaller than 3 cm, unless they require immediate surgery.
The HIF-2-alpha protein accumulates in patients when the tumor-suppressing von-Hippel-Lindau protein is inactivated, causing tumor growth. Inactivation of von-Hippel-Lindau occurs in more than 90% of clear cell renal cell carcinoma tumors.
This FDA based this decision, along with its decision to grant MK-6482 orphan drug designation for von Hippel-Lindau disease, on data from a phase 2 trial presented during the ASCO20 Virtual Scientific Program. Results showed 17 of 61 patients achieved a confirmed response to treatment for an overall response rate of 27.9% (95% CI, 17.1-40.8), with eight additional unconfirmed responses. Fifty-three patients (86.9%) demonstrated a reduction in target lesion size, and 98.3% achieved 12-month PFS.
The agent is currently being evaluated in a phase 3 trial for patients with advanced renal cell carcinoma (NCT04195750), a phase 2 trial for von Hippel-Lindau disease-associated renal cell carcinoma (NCT03401788), and a phase 1/phase 2 dose-escalation and dose-expansion trial for advanced solid tumors, including renal cell carcinoma (NCT02974738).
“Merck’s diverse and expansive oncology pipeline is focused on bringing forward innovative new treatments to patients in need and continues to show important progress,” Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, said in the release. “These designations for MK-6482 support the potential of targeting HIF-2-alpha in certain patients with von Hippel-Lindau disease, who currently have limited treatment options and face an increased risk for benign tumors, as well as several types of cancer, including renal cell carcinoma.”
- Jonasch E, et al. Abstract 5003. Presented at: ASCO20 Virtual Scientific Program; May 31-June 2, 2020.