Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced first-time results from a Phase 2 trial evaluating the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor MK-6482, a novel investigational candidate in Merck’s oncology pipeline, for the treatment of von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). In the trial, MK-6482 demonstrated durable responses with a confirmed objective response rate (ORR) of 27.9% (n=17/61) (95% CI: 17.1-40.8), and the median duration of response (DOR) was not yet reached (range: 9.1-39.0 weeks).
“Nobel Prize-winning research led to the discovery of HIF-2α and its role in cancer. MK-6482 was developed based on this science and with these data, we are seeing the potential of targeting HIF-2α in these patients who are in need of new options,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “These findings validate Merck’s long-term strategy for building the company’s oncology pipeline, including through the acquisition and accelerated development of novel therapeutic candidates such as MK-6482.”
“Von Hippel-Lindau disease is a rare hereditary condition affecting multiple organs, which puts patients at risk for several cancers, including renal cell carcinoma. Cancer remains one of the main causes of death for people with von Hippel-Lindau disease, and new treatment options are essential,” said Dr. Eric Jonasch, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The results of this study provide evidence of the potential benefit of MK-6482 and support further investigation into how this HIF-2α inhibitor could play a meaningful role for these patients, for whom there are currently no approved systemic therapy options available.”
These results are being presented in an oral abstract session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #5003). As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO20.
Study Design and Additional Data (Abstract #5003)
This study is a Phase 2, open-label, single-arm trial evaluating MK-6482 for the treatment of VHL-associated ccRCC (ClinicalTrials.gov, NCT03401788). The study enrolled adult patients with a pathogenic germline VHL variation, measurable localized or non-metastatic ccRCC, no prior systemic anti-cancer therapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Patients received MK-6482 120 mg orally once daily until disease progression, unacceptable toxicity, or investigator’s or patient’s decision to withdraw. The primary endpoint was ORR of VHL-associated ccRCC tumors per RECIST v1.1 by independent radiology review. Secondary endpoints included DOR, time to response, progression-free survival (PFS), and safety and tolerability.
As of data cut-off (December 6, 2019), 61 patients were enrolled in the study. Median duration of treatment was 36.1 weeks (range: 0-73), and 95.1% of patients were still on therapy. The results showed a confirmed ORR of 27.9% (n=17) (95% CI: 17.1-40.8); all responses were partial responses, and 43% of patients had stable disease. The median time to response was 23.7 weeks (range: 11.6-61.0), and median DOR was not yet reached (range: 9.1-39.0 weeks). Additionally, 86.9% (n=53) of patients had a decrease in size of target lesions.
Treatment-related adverse events (TRAEs) occurred in 96.7% of patients, with 9.8% being Grade 3. There were no Grade 4 or 5 TRAEs. The most common all-cause adverse events (≥20%) were anemia (86.9%), fatigue (57.4%), headache (36.1%), dizziness (31.1%) and nausea (24.6%). Grade 3 all-cause adverse events included fatigue (4.9%), anemia (3.3%), dyspnea (1.6%) and weight increase (1.6%).