Keytruda+Lenvima is an "immune + targeted" combination therapy that has been approved to treat 2 different types of cancer: endometrial cancer (EC), renal cell carcinoma (RCC).

Endometrial cancer (Image source: womenworking.com)

January 20, 2022 / Bio Valley BIOON/--Merck&Co and partner Eisai recently jointly announced the results of the pivotal Phase 3 clinical trial KEYNOTE-775/Study309 (NCT03517449) It has been published in the international medical journal "New England Journal of Medicine" (NEJM). The study evaluated the anti-PD-1 therapy Keytruda (generic name: pembrolizumab, pembrolizumab) in patients with advanced endometrial cancer (EC) who had previously received at least one platinum-based regimen Combination regimen with oral multi-receptor tyrosine kinase inhibitor Lenvima (Geneva, generic name: lenvatinib) and compared with chemotherapy (physician's choice of chemotherapy: doxorubicin or paclitaxel) . The results showed that compared with chemotherapy, the Keytruda+Lenvima regimen had statistically and clinically significant results in the primary endpoints of overall survival (OS) and progression-free survival (PFS), and the secondary endpoints of overall response rate (ORR). improve. See: Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.

Keytruda + Lenvima is an "immune + targeted" combination therapy, the first immunotherapy + tyrosine kinase inhibitor combination regimen approved for the treatment of EC. The combination is currently approved in Japan, the United States, and Europe for adults with certain types of advanced endometrial cancer (EC). In addition, the combination is approved for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in the US and EU.

In the treatment of EC, in the United States, the Keytruda+Lenvima regimen is suitable for the treatment of: disease progression after receiving systemic therapy in any case, not suitable for radical surgery or radiotherapy, and not confirmed by testing to be microsatellite hyperinstability (MSI-H) or advanced endometrial cancer (EC) patients who are not mismatch repair deficient (dMMR). Here, "not MSI-H or not dMMR" is also referred to as "non-microsatellite high instability (non-MSI-H) or mismatch repair normal (pMMR)". In the European Union and Japan, the Keytruda+Lenvima regimen is indicated for the treatment of adult patients with advanced or recurrent endometrial (EC) cancer who have progressed on prior platinum-containing regimens in any setting and are not candidates for radical surgery or radiotherapy.

KEYNOTE-775/Study309 study PFS and OS data (click image for larger image)

KEYNOTE-775/Study309 is a pivotal Phase 3 clinical trial evaluating Keytruda in 827 patients (697 pMMR, 130 dMMR) with advanced EC who had previously received at least one platinum-containing chemotherapy regimen Efficacy and safety of the +Lenvima regimen.

The results showed that, compared with chemotherapy (doctor's choice: doxorubicin or paclitaxel), the Keytruda+Lenvima regimen had statistically significant and clinically significant improvements in the primary endpoints of OS and PFS, and the secondary endpoints of ORR. The specific data are as follows:

——OS was significantly prolonged: (1) pMMR population (median OS: 17.4 months vs 12.0 months), 32% lower risk of death (HR=0.68, p<0.001); (2) overall population (median OS: 17.4 vs 12.0 months) OS: 18.3 months vs 11.4 months), and a 38% lower risk of death (HR=0.62, p<0.001).

——PFS significantly prolonged: (1) pMMR population (median PFS: 6.6 months vs 3.8 months), a 40% reduction in the risk of disease progression or death (HR=0.60, p<0.001); (2) overall There was a 44% reduction in the risk of population (median PFS: 7.2 months vs 3.8 months), disease progression, or death (HR=0.56, p<0.001).

—— Significantly improved ORR: (1) pMMR population (ORR: 30.3% vs 15.1%; complete remission [CR]: 5.2% vs 2.6%); (2) overall population (ORR: 31.9% vs 14.7 %; CR: 6.6% vs 2.6%).

In terms of safety, 88.9% of patients who received Keytruda + Lenvima had adverse events of grade 3 or above; among patients who received chemotherapy, 72.7% of patients experienced adverse events of grade 3 or above.

The Keytruda+Lenvima combination therapy is part of a strategic collaboration between Merck & Co. and Eisai Oncology. In March 2018, the two parties signed a cooperation agreement totaling up to $5.8 billion to develop Lenvima as a single drug and in combination with Keytruda for the treatment of various types of tumors.

Lenvima is an oral multi-receptor tyrosine kinase (RTK) inhibitor with a novel binding mode, in addition to inhibiting other pro-angiogenic and oncogenic signaling pathway-related RTKs involved in tumor angiogenesis, tumor progression, and tumor immune modification, including In addition to platelet-derived growth factor (PDGF) receptors (PDGFRα, KIT and RET), it also selectively inhibits vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2, VEGFR3) and fibroblast growth factor (FGF) receptors. Kinase activity of the body (FGFR1, FGFR2, FGFR3, FGFR4).

Keytruda is an anti-PD-1 tumor immunotherapy that helps detect and fight tumor cells by boosting the body's immune system's ability. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that can affect tumor cells and healthy cells.

Currently, Eisai and Merck are conducting LEAP (LEnvatinib and Pembrolizumab) clinical development programs in more than 10 different tumor types (endometrial cancer, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma) The Lenvima + Keytruda combination continues to be studied in more than 20 clinical trials in squamous cell carcinoma, urothelial carcinoma, cholangiocarcinoma, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, pancreatic cancer, and triple-negative breast cancer. Data from the program show that the Lenvima + Keytruda combination has demonstrated strong efficacy in multiple tumor types. (Bioon.com)