New drug for renal cancer! Mk-6482 has obvious advantages in the treatment of clear cell renal cell carcinoma

Researchers from Dana Farber Cancer Institute recently published the results of an I / II clinical trial (nct02974738) of mk-6482 in the treatment of advanced clear cell renal cell carcinoma (ccrcc) at the 2020 American Society of clinical oncology urogenital cancer symposium (ASCO-GU 2020) held in San Francisco The study was conducted in 55 patients who had previously received a median of 3 systemic therapies, the vast majority of whom received VEGF inhibitors (93%) and immunocheckpoint inhibitors (73%), and two-thirds of whom received anti-PD-1 and anti VEGF therapies The results show that in this group of refractory patients, mk-6482 single drug treatment has achieved very promising efficacy data: in all risk categories, the total response rate (ORR) is 24%, and the disease control rate is 80% In most (about 90%) ccrcc patients, an anti-tumor protein called von Hippel Lindau (VHL) does not work, resulting in the accumulation and activation of hypoxia inducible factor (HIF) protein in cancer cells, mistakenly signaling hypoxia, which can activate angiogenesis and stimulate tumor growth Mk-6482 (formerly pt2977) is a kind of drug targeting to inhibit hypoxia inducible factor-2A, which can block cell growth, proliferation and prevent abnormal angiogenesis Mk-6482 is developed by petrolon therapeutics, and MSD acquired petrolon therapeutics with a down payment of US $1.05 billion and a milestone payment of US $1.15 billion in May 2019 In the study published at the meeting, the median follow-up period was 13 months, 13 patients were in remission, the overall remission rate (ORR) was 24% (n = 13 / 55), and 31 patients were stable The disease control rate (DCR = complete remission + partial remission + stable disease) was 80% (n = 44 / 55) Among 55 patients, 38 (69%) had tumor shrinkage Remission was observed in low, medium and high-risk patients: 2 of 5 low-risk patients, 10 of 40 medium-risk patients and 1 of 10 high-risk patients Partial remission was achieved after mk-6482 treatment The median duration of remission (DOR) has not yet been achieved 81% of patients with remission had dor ≥ 6 months, and 16 patients (29%) had continued treatment for more than 12 months Overall, mk-6482 resulted in a median progression free survival (PFS) of 11 months and a 12-month progression free survival of 49% The median PFS was 16.5 months, 11.0 months and 6.9 months in the low, medium and high-risk groups, respectively In the study, mk-6482 showed good tolerance, safety and single drug therapeutic activity The results of this study support the planned phase III trial (nct04195750) The trial will be carried out in patients with metastatic ccrcc who have previously received PD-1 / PD-L1 inhibitors and VEGF targeted therapies, with no more than three systemic therapies 736 patients are planned to be enrolled in the study In the study, patients will be allocated to mk-6842 single drug treatment or afinitor single drug treatment in a ratio of 1:1 The common main end points of the study are total survival (OS) and progression free survival (PFS) First author of the research abstract, director of ranker urogenital tumor center, Dana Farber Cancer Institute, Jerome and Nancy Kohlberg medical professor Toni, Harvard Medical School "For a new drug as a single drug therapy, the total response rate in all risk categories, whether low, medium, high risk or in the severely refractory population, is 24%, which is very promising," choueiri said Choueiri's mentor and co-author, William g kaelin Jr., shared the 2019 Nobel Prize in medicine with two other researchers, who revealed the mechanism by which the human body senses oxygen levels and activates related genes to adapt to hypoxia Clear cell renal cell carcinoma (ccrcc) is a kind of tumor characterized by malignant epithelial cells It has clear cytoplasm, dense nest like growth, and complicated dendritic vessels According to Medscape, the incidence rate of RCC has been rising in Europe and the United States over the past 30 years, and the incidence rate of the disease is higher than that of women The typical age of diagnosis of ccrcc is 60-64 years old, but 7% of sporadic ccrcc is diagnosed in the population under 40 years old The most common risk factors are smoking, obesity and high blood pressure Dana Farber researchers present promising kidney cancer trial results