Merck’s KEYTRUDA Demonstrates 38% Improvement in Overall Survival as Adjuvant Therapy in Phase 3 KEYNOTE-564 Trial for Renal Cell Carcinoma

Jan 30, 2024 08:00 CST Updated 08:01

MSD

Pharmaceutical R&D and Manufacturer

▎Edited by the WuXi AppTec content team

Recently, MSD released the latest results of the Phase 3 clinical trial KEYNOTE-564,This trial evaluated the treatment effect of anti-PD-1 therapy Keytruda as an adjuvant treatment for patients with renal cell carcinoma (RCC) who have intermediate-high or high risk of recurrence after nephrectomy, or after nephrectomy and resection of metastatic lesions.. The latest data shows,Keytruda as an adjuvant therapy significantly improved the overall survival (OS) of RCC patients by up to 38%.

KEYNOTE-564 is a randomized, double-blind Phase 3 clinical trial,To evaluate the adjuvant treatment effect of Keytruda in RCC patients who have undergone nephrectomy and whose disease is at intermediate-high risk, high risk, or M1 with no evidence of disease (NED). The primary endpoint of the trial is disease-free survival (DFS) assessed by investigator review, and secondary endpoints include OS and safety.The study enrolled a total of 994 patients who were randomized 1:1 to receive either Keytruda (200 mg intravenously on Day 1 of each 3-week cycle for up to 17 cycles) or placebo (normal saline intravenously on Day 1 of each 3-week cycle for up to 17 cycles).

At the third pre-specified interim analysis (median follow-up time was 57.2 months, ranging from 47.9 to 74.5 months),Keytruda as adjuvant therapy significantly improved overall survival — this was the primary secondary endpoint of the trial, with a 38% increase compared to placebo (HR=0.62, [95% CI, 0.44-0.87]; P=0.002).At 48 months, the estimated OS rate for patients treated with Keytruda was 91.2%, while the OS rate for patients treated with placebo was 86.0%.

Image Source:123RF

According to previous reports, in the early pre-specified interim analysis with a median follow-up time of 24.1 months, KEYNOTE-564 reached the primary endpoint of disease-free survival.Compared with placebo, the risk of disease recurrence or death was reduced by 32% (HR=0.68, [95% CI, 0.53-0.87]; one-sided P=0.001).In the third interim analysis, the DFS benefit was consistent with previously reported data, compared to placebo,Keytruda as an adjuvant therapy reduced the risk of disease recurrence or death by 28% (HR=0.72, [95% CI, 0.59-0.87]).

Based on the DFS data from KEYNOTE-564, which was first presented at the 2021 ASCO Annual Meeting, Keytruda has been approved in the United States, the European Union, Japan, and other countries and regions around the world for adjuvant treatment of RCC patients. MSD is currently working with health authorities to incorporate these OS data into the full prescribing information for Keytruda.

MSD has launched an extensive RCC clinical development program across various settings, including adjuvant and advanced disease, utilizing Keytruda as a monotherapy or in combination with Welireg (belzutifan, MSD's oral hypoxia-inducible factor-2α inhibitor), Lenvima (lenvatinib, a multi-target VEGF tyrosine kinase inhibitor), and quavonlimab (a CTLA-4 monoclonal antibody).

Keytruda is a humanized anti-PD-1 monoclonal antibody that blocks the binding of PD-1 to its ligands PD-L1 and PD-L2, thereby activating T lymphocytes.This effect may enhance the ability of the immune system in the body to detect and resist tumor cells. In September 2014, Keytruda was first approved by the FDA for the treatment of advanced melanoma and was subsequently approved as a first-line therapy for patients with metastatic non-small cell lung cancer (NSCLC). In China, Keytruda has also been approved for multiple indications.

The safety profile of Keytruda was consistent with previously reported study results, and no new safety signals were identified.Treatment-related adverse events (TRAEs) occurred in 79.1% (n=386) of patients in the Keytruda group and 53.0% (n=263) of patients in the placebo group. The incidence of grade 3-4 TRAEs was 18.6% in the Keytruda group and 1.2% in the placebo group. Treatment was discontinued due to TRAEs in 18.2% of patients in the Keytruda group and 0.8% of patients in the placebo group, with no treatment-related deaths reported in either group.

From January 31 to February 1, 2024, we will launch a limited-time online replay of the "2024 WuXi AppTec Global Forum."Across time and space, allowing colleagues from all over the world to "zero-distance" listen to wonderful viewpoints, seize opportunities, and gain insights into the future! This article offers a sneak peek at some of the golden words and wise sayings from the guests, giving everyone an early look. Welcome to scan the QR code below to register and reserve to watch more exclusive insights!

▲This forum is free and open to a global audience. Press and hold to scan the QR code above to apply for viewing. To meet the viewing needs of different regions around the world, this event will offer subtitled versions and multiple suitable broadcast times.

Everyone is watching

▲To learn more about the application of cutting-edge technologies in the biopharmaceutical industry, please long-press and scan the QR code above to access "WuXi Live Studio" and watch live discussions and exciting replays on related topics.

References:

[1] Merck’s KEYTRUDA® (pembrolizumab) Reduced the Risk of Death by 38% Versus Placebo as Adjuvant Therapy for Patients With Renal Cell Carcinoma (RCC) at an Increased Risk of Recurrence Following Nephrectomy，Retrieved January 29, 2024 from https://www.businesswire.com/news/home/20240127244606/en

Disclaimer: The content team of WuXi AppTec focuses on introducing the research progress in global biopharmaceuticals and health. This article is for information exchange purposes only, and the views expressed in the article do not represent the position of WuXi AppTec, nor does it indicate that WuXi AppTec supports or opposes these views. This article is not a recommendation for treatment plans. For guidance on treatment options, please visit a正规 hospital.

Copyright Statement: This article is from the content team of WuXi AppTec. Individuals are welcome to share it on their social media platforms, but unauthorized reproduction by media or institutions in any form to other platforms is prohibited. For authorization to reproduce, please reply with "reprint" on the WeChat Official Account of "WuXi AppTec" to obtain reprint guidelines.

Share，PointLike，In view, Focusing on Global Biomedical Health Innovation