May 26, 2024

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Renal cell carcinoma (RCC): Lenvima + Keytruda with strong efficacy!

Renal cell carcinoma (RCC): Lenvima + Keytruda with strong efficacy!


Renal cell carcinoma (RCC): Lenvima + Keytruda with strong efficacy!  Renal cell carcinoma (RCC) “targeted + immune” treatment! Lenvima + Keytruda (lenvatinib + pembrolizumab) showed strong efficacy!

Renal cell carcinoma (RCC): Lenvima + Keytruda with strong efficacy!
Kidney cancer (Image source:


Recently, Eisai’s oral multi-receptor tyrosine kinase inhibitor Lenvima (generic name: lenvatinib, lenvatinib) and Merck’s anti-PD-1 therapy Keytruda (generic name: pembrolizumab, pembrolizumab) was evaluated in combination therapy The results of the Phase 1b/2 clinical study of renal cell carcinoma (RCC) (Study 111/KEYNOTE-146) were published in 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 show that in patients with metastatic RCC who have not previously received treatment (initial treatment) and have received treatment (treatment, including immune checkpoint inhibitor [ICI]), the “targeted + immune” treatment plan Lenvima + Keytruda Shows encouraging anti-tumor activity and controllable safety.

At present, the supplementary new drug application (sNDA) and supplementary biological product license application (sBLA) of the Lenvima+Keytruda combination regimen for the first-line treatment of advanced RCC are undergoing priority review by the US FDA. The target dates for the Prescription Drug User Fee Act (PDUFA) are 2021, respectively. August 25th and 26th.

The results from the key Phase 3 CLEAR study (Study 307/KEYNOTE-581) showed that: in the first-line treatment of patients with advanced RCC, compared with sunitinib treatment group, Lenvima+Keytruda treatment group was in the primary endpoint (no Progressive survival, median PFS: 23.9 months vs 9.2 months; HR=0.39, p<0.001), overall survival for key secondary endpoints (median OS: not reached vs not reached; HR=0.66; p=0.005 ) And objective remission rate (ORR: 71.0% vs 36.1%; p<0.001) both have statistically significant and clinically significant improvements.


Renal cell carcinoma (RCC): Lenvima + Keytruda with strong efficacy!



Study 111/KEYNOTE-146 RCC cohort trial design and data:

Study 111/KEYNOTE-146 (NCT02501096) is an open-label Phase Ib/II study, in the age of 18 years or older, with selected solid tumors, the Eastern Cooperative Oncology Group (ESOG) physical performance status (PS) score is 0- It was carried out in 1 patients, and the efficacy and safety of the Lenvima+Keytruda combination regimen were evaluated. In the study, patients received Lenvima (20 mg, orally, once a day) and Keytruda (200 mg, intravenous infusion, once every 3 weeks) treatment until the disease progressed, unacceptable toxicity appeared or the informed consent was withdrawn.

The results published in the “Lancet Oncology” article analyzed the efficacy of patients with metastatic clear cell renal cell carcinoma (ccRCC), and were grouped according to previous treatments: initial treatment (no previous treatment), after treatment ICI initial treatment (previously received at least one therapy but no immune checkpoint inhibitor [ICI] treatment), ICI treated (previously received ICI treatment). The safety analysis was performed on all patients enrolled and treated. The primary endpoint is the objective response rate (ORR) at week 24 determined by the research investigator based on the immune-related solid tumor efficacy evaluation criteria (irRECIST).

Between July 21, 2015 and October 16, 2019, 145 patients were included in the study. Two patients with non-clear cell renal cell carcinoma were excluded from the efficacy analysis (1 from the naive group and 1 from the ICI treated group); therefore, the population evaluated for efficacy included 143 patients (the naive group) n=22, n=17 in the treated ICI initial treatment group, n=104 in the ICI treated group). All 145 enrolled patients were included in the safety analysis.

The median follow-up was 19.8 months (IQR 14.3-28.4). The primary endpoint data showed that in the 24th week of treatment, the ORR of the initial treatment group was 72.7% (n=16/22), the ORR of the treated ICI initial treatment group was 41.2% (n=7/17), and the ORR of the ICI treated group was 55.8% (n=58/104).

In terms of safety, of the 145 patients, 82 (57%) had Grade 3 treatment-related adverse events (TRAE), and 10 patients (7%) had Grade 4 TRAE. The most common grade 3 TRAE is hypertension (30 out of 145 patients, 21%). Thirty-six patients (25%) had severe TRAE, and there were 3 treatment-related deaths (upper gastrointestinal bleeding, sudden death, and pneumonia).

The results of the study confirmed that the Lenvima+Keytruda combination regimen showed encouraging anti-tumor activity and controllable safety. For patients with metastatic RCC, including patients treated with ICI, Lenvima+Keytruda can be used 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 of women. Most RCCs are accidentally discovered during imaging examinations of other abdominal diseases. Approximately 30% of RCC patients have metastatic disease at the time of diagnosis, and up to 40% of patients will have metastases after local RCC surgery. The survival rate is highly dependent on the stage at the time of diagnosis. The 5-year survival rate of patients with metastatic disease is only 13%, and the prognosis is very poor.

Lenvima+Keytruda combination therapy is part of the strategic cooperation between Eisai and Merck Oncology. In March 2018, Merck and Eisai signed a total cooperation agreement of up to 5.8 billion U.S. dollars to develop a single drug of Lenvima and a combination with Keytruda for the treatment of multiple types of tumors.

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

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, thereby activating T lymphocytes that may affect tumor cells and healthy cells.

At present, Merck and Eisai are conducting the LEAP (LEnvatinib and Pembrolizumab) clinical development project in 14 different types of tumors (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-negative breast cancer) continue to study Lenvima+Keytruda combination in 20 clinical trials. Data from this project shows that the combination of Lenvima+Keytruda has shown strong efficacy in multiple types of tumors.




(source:internet, reference only)

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