MK-6482, the next rising anticancer drug is being developing

Dana-Farber Cancer Institute-MSD merged to develop HIF-2α inhibitor

Phase III clinical trials was started for kidney cancer. Six university hospitals participated

The development of the next generation of targeted anticancer drugs, which combines the Nobel Prize-winning theory with the field of chemotherapy, is entering the second half.

 

The first is about the ​​advanced renal cell carcinoma.

 

Von Hippel-Lindau (VHL) works by the Dana-Farber Cancer Institute, winner of the 2019 Nobel Prize in Medicine, revealing a new mechanism by which the 'defective protein' is involved in cancer development.

 

The main character is a substance that intensively targets 'HIF-2α' generated in patients with VHL deficiency in collaboration with MSD, a multinational pharmaceutical company.

 

It is noteworthy that the drug is a first-in-class product that has elicited an overall response rate of 24% in patients who were previously unresponsive to treatment with VEGF inhibitors or immune checkpoint inhibitors.

 

The first clinical data for the next generation of targeted anticancer drugs in advanced renal cell carcinoma was released on the 18th at the Genitourinary Cancers Symposium (GUCS).

 

First, the substance is an oral target anticancer drug developed by MSD and is called MK-6482.

 

And this is a once-daily formulation that has a mechanism of action that targets HIF-2α, which is involved in the production of new angiogenesis that supplies nutrients to renal tumors.

 

This is the first therapeutic agent (first in class) among the oral HIF-2α inhibitors.

 

Clinical data from this 13-month follow-up (median) reported a 24% overall response to treatment in the patient group receiving the test substance.

 

The key is that 55 patients who responded to MK-6482 had previously been diagnosed with advanced clear cell renal cell carcinoma and had advanced experience in chemotherapy.

 

In particular, they were patients who used PD-1/L1 family of immune checkpoint inhibitors, including VEGF inhibitor family of target anticancer agents, before MK-6482.

 

Toni Choueiri, Ph.D., author of the Dana-Farber Cancer Institute, said in a recent report that the response rates reported in these late-stage trials are remarkable, the anticancer drugs in the renal cancer field fail repeatedly in major clinical trials, and that the situation is expected to show good results in improving PFS.

 

Professor Toni Choueiri said, "In transparent cell renal cell carcinoma, about 90% of patients show a defect in a specific protein called von Hippel-Lindau (VHL), and VHL deficiency eventually promotes HIF protein activation and accelerates cancer progression by promoting angiogenesis in tumor cells".

 

"This is a collaborative study with William Kaelin Jr., Ph.D.

 

of the Dana-Farber Cancer Institute, which won the Nobel Prize in medicine last year for VHL-related research, and it shows the development of MK-6482, the first HIF-2α inhibitor".

 

Phase III clinical trials begin, with 22 patients in 6 domestic hospitals In Phase I/II clinical trials, 55 patients with advanced renal cell carcinoma at the age of 63 years (medium) with previous experience with chemotherapy were enrolled.

 

Thirty-nine (71%) of these patients eventually discontinued treatment, with cancer progressing (55%) in most cases.

 

In the interim analysis, 81% of patients treated had expected response rates for more than six months, and 29% had been treated for more than 12 months.

 

The median progression free survival (PFS), an important criterion, was 11 months.

 

In terms of safety, four patients died of disease-related adverse events during the study, but none of the treatment-related adverse events occurred.

 

Grade 3~5 to adverse events were observed in 65% of the patients, five of whom had to reduce the dose due to toxicity issues.

 

Phase III clinical trial is a comparative study with anti-cancer drug 'Everolimus', and PFS is a major evaluation index, and it has entered full-scale clinical trials.

 

In Korea, the same phase III clinical trials have begun in full-scale clinical trials in February, after approval by the Ministry of Food and Drug Safety.

 

In relation to MK-6482, label disclosure, randomization, and phase III clinical trial studies submitted by MSD Korea will be followed by a late phase clinical trial comparing MK-6482 to Everolimus in patients with advanced renal cell carcinoma who have experienced disease progression after PD-1 / L1 and VEGF-targeted therapies.

 

Starting from February of this year, it is scheduled to proceed until September 2025, and 22 patients will be participating in the registration of 736 global clinical patients.

 

Meanwhile, MK-6482's post-clinical domestic participatory hospitals will be held in six locations including Chungnam National University Hospital, National Cancer Center, The KUMC, Yonsei Severance Hospital, Samsung medical center, and Asan medical center.