Immunotherapy for advanced liver cancer! Priority review of Bristol Myers Squibb oy portfolio in the US

On November 11, BMS announced that FDA has accepted a supplementary biological product license application (SBLA) submitted by BMS, and awarded the breakthrough drug qualification of opdivo and yevoy combined immunotherapy (oy) for the treatment of advanced liver cell carcinoma (HCC) patients who have received sorafenib treatment in the past FDA has granted the SBLA priority review, with PDUFA target date of March 10, 2020 Liver cancer is the fourth leading cause of cancer death in the world, and HCC is the most common type of liver cancer, which is also the cause of the fastest rise in cancer-related deaths Sorafenib, an oral kinase inhibitor of Bayer, was approved by FDA in November 2007 It is currently the first-line standard nursing drug for HCC In April 2017, stivarga, another oral multi kinase inhibitor of Bayer, was approved by FDA, becoming the first new liver cancer drug in the U.S market in recent ten years, which was used for the second-line treatment of HCC patients who had previously received sorafenib treatment (sorafenib) At present, liver cancer has become a hot spot in the research and development of new drugs According to the search results of FDA new drug database, 6 drugs were approved to treat HCC in 2017-2019 In addition to stivarga, it also includes opdivo (September 2017, sorafenib treated patients), lenvima (June 2018, first-line treatment), keytruda (November 2018, sorafenib treated patients), cabometyx (January 2019, sorafenib treated patients), cyramza (may 2019, sorafenib treated patients with high alpha fetoprotein expression) Among these drugs, stivarga, lenvima and cabometyx are kinase inhibitors, opdivo and keytruda are PD - (L) 1 tumor immunotherapy, and cyramza is McAb type angiogenesis inhibitors The two drugs in the oy combination are tumor immunotherapy By targeting different regulatory elements in the immune system, the human body's own immune system is used to fight against tumors Opdivo targeted to block the PD-1 / PD-L1 pathway, while yevoy targeted to block CTLA-4 The oy combination is the most important treatment option in the BMS oncology pipeline, and in addition to HCC, the company is evaluating the combination for many other types of tumors This SBLA is based on the oy cohort results of the I / II checkmate-040 (nct01658878) study This is an ongoing open label, multi cohort study in patients with advanced HCC who have not previously been treated with sorafenib (first treatment with sorafenib), or who are intolerant to sorafenib, or who have progressed during sorafenib treatment, with or without viral hepatitis, investigating the efficacy and safety of opdivo or opdivo based combination therapy The oy cohort is evaluating three dosing regimens: group A: opdivo 1mg / kg and yevoy 3mg / kg combination regimens (o1y3) once every three weeks (q3w) for four cycles, followed by opdivo 240mg once every two weeks (q2w); group B: opdivo 3mg / kg and yevoy 1mg / kg combination regimens (o3y1) for four cycles, followed by opdivo 240mg (q2w); group C: opdivo 3mg / kg q2w and yevoy 1mg / kg once every 6 weeks (Q6W) The first data of the study has been published at the 2019 ASCO annual meeting The data showed that the lowest follow-up period was 28 months The objective response rate was 31% and the median response duration was 17.5 months (95% CI: 11.1-n / a) Significant remission was observed in all three treatment groups, of which group a experienced the longest median OS in the cohort, 22.8 months (95% CI: 9.4-n / a) and 30 months (95% CI: 29.5-57) The disease control rates of the three groups were 54%, 43% and 49%, respectively In the entire cohort, 5% of patients achieved complete remission, and 26% achieved partial remission, regardless of baseline tumor PD-L1 status In the study, oy combination showed acceptable safety, and no new safety signal was generated in each treatment group