"Target + immune"! The first result of the $5.8 billion cooperation between MSD and Weicai: lenvima + keytruda combination has been approved by the US FDA!

September 18, 2019 / BIOON / - Eisai and Merck & Co recently jointly announced that FDA ）The combination therapy of lenvima (Chinese brand name: lewima, generic name: lenvatinib, lovatinib mesylate) and keytruda (Chinese brand name: coreda, generic name: pembrolizumab, mAb) has been approved for the treatment of patients with advanced endometrial cancer, specifically: not MSI-H or Patients with mismatch repair defect (dmmr), disease progression after previous systematic treatment, and not suitable for radical surgery or radiotherapy After the application was filed on June 17, the FDA conducted a review through the RTOR pilot project, which aims to improve the efficiency of the review to ensure that treatment drugs are provided to patients as early as possible RTOR allows applicants to review most of the data in advance before submitting a full application This approval is accelerated, and further ongoing approval may depend on the validation and description of clinical benefits in a confirmatory clinical trial According to the FDA, the review was conducted under the Orbis program, an initiative of the FDA cancer center of excellence The Orbis project provides a framework for international partners to submit and review cancer drugs simultaneously Under this program, FDA, TGA and Health Canada jointly reviewed the applications of two cancer drugs, allowing simultaneous decisions in all three countries This approval is based on data from study 111 / keynote-146 This is a multi cohort, multi center, open label, single arm phase II study involving 108 patients with metastatic endometrial cancer who have progressed after at least one systematic treatment In 94 patients with non MSI-H or dmmr, the overall response rate (ORR) was 38.3% (95% CI: 29-49), the complete response rate (CR) was 10.6% (n = 10), and the partial response rate (PR) was 27.7% (n = 26) Among the patients with remission identified by independent review (n = 36), the median dor (range 1.2 + to 33.1 + months) had not been reached by the end of the data period, and 69% of the patients had remission lasting for 6 months or longer The most common side effects of lenvima + keytruda combination (> 20%) were fatigue, musculoskeletal pain and hypertension Diarrhea, loss of appetite, hypothyroidism, nausea, stomatitis, vomiting, weight loss, abdominal pain, headache, constipation, urinary tract infection, dyspepsia, dysphonia, bleeding events, hypomagnesemia, red cell sensation disorder of palms and soles, dyspnea, cough and rash It is worth mentioning that this approval is also the first approval of lenvima and keytruda in terms of us regulation At present, Weicai and MSD are working together to develop the combination for multiple types of cancer Previously, FDA Three breakthrough drug qualifications (BTD) have been granted to the combination, which are: (1) treatment of advanced and / or metastatic microsatellite stability (MSS) / mismatch repair normal (MMR) endometrial cancer (EC); (2) treatment of advanced and / or metastatic renal cell carcinoma (RCC); (3) first-line treatment of advanced unresectable liver cancer (HCC) which is not suitable for local area treatment Lenvima + keytruda combination therapy is part of the strategic cooperation between MSD and Weicai oncology In March 2018, the two sides signed a cooperation agreement with a total amount of US $5.8 billion to develop lenvima single drug and a combination of drugs with keytruda for the treatment of various types of tumors In addition to the ongoing evaluation of the combination of lenvima and keytruda in the treatment of several different types of tumors, including renal cell carcinoma, the two sides also launched the leap clinical project to evaluate 11 treatment indications of six types of cancer (endometrial carcinoma, liver cell carcinoma, melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma) The leap clinical program also includes a new basket study of six additional cancer types (cholangiocarcinoma, triple negative breast cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer) Lenvatinib is a kind of targeted drug discovered and developed by Weicai It is an oral multi receptor tyrosine kinase (RTK) inhibitor with novel binding mode In addition to inhibition of tumor angiogenesis, tumor progression and tumor In addition to other angiogenic and carcinogenic signaling pathway related RTK (including PDGF receptor PDGFR α, kit and RET), immunomodified RTK can selectively inhibit the kinase activities of VEGF receptor (VEGFR1, VEGFR2, VEGFR3) and fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3, FGFR4) Keytruda is an anti-PD-1 tumor immunotherapy that helps detect and fight tumor cells by improving the ability of the human immune system Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thus activating T lymphocytes that may affect tumor cells and healthy cells PD - (L) 1 immunotherapy is a kind of tumor immunotherapy, which aims to use the body's own immune system to resist cancer, and block the PD-1 / PD-L1 signal pathway to make cancer cells die So far, nine PD - (L) 1 tumor immunotherapies have been approved worldwide, among which keytruda is the leader in this field MSD has the largest clinical research project of immunotumor in the industry At present, there are more than 1000 clinical trials studying keytruda in various cancer and treatment environments The project aims to understand the role of keytruda in cancer treatment and predict the factors that patients can benefit from keytruda treatment, including exploring several different biomarkers In June, MSD held its first investor day meeting in five years and said that keytruda's approved indications are expected to more than double in the next five years Original source: FDA approvals lennima? (lenvatinib) plus keytruda? (pembrolizumab) combination treatment for patients with certain types of endogenetic carinoma