Lenvima plus Keytruda Demonstrates Robust Efficacy in Renal Cell Carcinoma with Targeted and Immunotherapy Combination

Kidney cancer (Image source: vecteezy.com)

June 21, 2021 /BioonBIOON/ -- Recently, the results of a Phase 1b/2 clinical study (Study 111/KEYNOTE-146) evaluating the combination of Eisai's oral multi-receptor tyrosine kinase inhibitor Lenvima (Chinese trade name: Lenvima, generic name: lenvatinib) and MSD's anti-PD-1 therapy Keytruda (Chinese trade name: Keytruda, generic name: pembrolizumab) for the treatment of renal cell carcinoma (RCC) were published in 《The Lancet·Tumorology》 (The Lancet Oncology). The title of the article is:Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study。

The results showed,In previously untreated (treatment-naïve) and previously treated (treatment-experienced, including immune checkpoint inhibitors [ICI]) patients with metastatic RCC, the "targeted therapy + immunotherapy" regimen of Lenvima + Keytruda showed encouraging anti-`Tumor`Efficacy and manageable safety.

Study 111/KEYNOTE-146 RCC Cohort Trial Design and Data:

Study 111/KEYNOTE-146 (NCT02501096) is an open-label Phase Ib/II study in patients aged ≥18 years with selected solid tumors, EasternTumorConducted in patients with a Performance Status (PS) score of 0–1 in the ESOG, the study evaluated the efficacy and safety of the Lenvima plus Keytruda combination regimen. In the study, patients received Lenvima (20 mg orally once daily) and Keytruda (200 mg intravenously once every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal of informed consent.

《The Lancet·TumorBased on the results published in the 》 article, efficacy analysis was conducted on patients with metastatic clear cell renal cell carcinoma (ccRCC), stratified by prior treatment: treatment-naïve (no prior therapy), previously treated but ICI-naïve (received at least one prior therapy but no immune checkpoint inhibitor [ICI] therapy), and ICI-experienced (received prior ICI therapy). A safety analysis was performed on all enrolled and treated patients. The primary endpoint was the objective response rate (ORR) at Week 24, as assessed by study investigators according to the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).

Between July 21, 2015, and October 16, 2019, 145 patients were enrolled in the study. Two patients with non-clear cell renal cell carcinoma were excluded from the efficacy analysis (one from the treatment-naive group and one from the ICI-pretreated group); therefore, the efficacy-evaluable population comprised 143 patients (treatment-naive group, n=22; previously treated, ICI-naive group, n=17; ICI-pretreated group, n=104). All 145 enrolled patients were included in the safety analysis.

Regarding safety, 82 of 145 patients (57%) experienced grade 3 treatment-related adverse events (TRAEs), and 10 (7%) experienced grade 4 TRAEs. The most common grade 3 TRAE wasHypertension(30 of 145 patients, 21%). Severe TRAEs occurred in 36 patients (25%), with 3 treatment-related deaths (upper gastrointestinal bleeding, sudden death, and pneumonia).

The study results confirm that the Lenvima + Keytruda combination regimen demonstrates promising anti-Tumoractivity and a manageable safety profile. For patients with metastatic RCC, including those previously treated with ICIs, the Lenvima + Keytruda regimen may serve as a potential treatment option.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of kidney cancer cases. The incidence of RCC in men is approximately twice that in women. Most RCCs are discovered incidentally during imaging studies for other abdominal conditions. Approximately 30% of RCC patients present with metastatic disease at diagnosis, and up to 40% of patients develop metastases after surgical treatment for localized RCC. Survival rates are highly dependent onDiagnosisAt the time of staging, the 5-year survival rate for patients with metastatic disease is only 13%, indicating a very poor prognosis.

The Lenvima + Keytruda combination therapy is part of Eisai and MSD's strategic collaboration in oncology. In March 2018, MSD and Eisai signed a collaboration agreement valued at up to $5.8 billion to develop Lenvima as a monotherapy and in combination with Keytruda for various types...Tumortreatment of.

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

Keytruda is an anti-PD-1 cancer immunotherapy that helps detect and fight tumor cells by enhancing the body's immune system. 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 may affectTumorT lymphocytes of cells and healthy cells.

Currently, MSD and Eisai are conducting the LEAP (Lenvatinib and Pembrolizumab) clinical development program across 14 different tumor types (endometrial cancer, hepatocellular carcinoma,Melanoma、non-small cell lung cancer、renal cell carcinoma、head and neck squamous cell carcinoma、urothelial carcinoma、cholangiocarcinoma、colorectal cancer、gastric cancer、glioblastoma、ovarian cancer、pancreatic cancer and triple-negativeBreast Cancer) of the 20 itemsClinical Trial...continued to study the Lenvima + Keytruda combination. Data from this study show that the Lenvima + Keytruda combination has already in multiple typesTumordemonstrated robust efficacy. (Bioon.com)

Original Source:Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study