Approval

Mercks Keytruda Gets European Approval As Adjuvant Therapy For Certain Patients With RCC Following Surgery

January 28,2022 10:29 AM
- By Admin

Merck, known as MSD outside the United States and Canada, announced that the European Commission has approved Keytruda, Merck’s anti-PD-1 therapy, as monotherapy for the adjuvant treatment of adults with renal cell carcinoma (RCC) at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. This approval is based on results from the phase 3 KEYNOTE-564 trial, in which Keytruda demonstrated a statistically significant improvement in disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) after a median follow-up of 23.9 months compared to placebo, in patients at increased risk of recurrence (defined in the clinical trial protocol as intermediate-high or high risk following nephrectomy and those with resected advanced disease).

“Keytruda addresses a critical unmet need for treatment options that help patients reduce their risk of cancer returning following surgery,” said Dr. Thomas Powles, professor of Genitourinary Oncology and director of Barts Cancer Centre at St. Bartholomew’s Hospital. “The European Commission’s approval of Keytruda brings certain patients with renal cell carcinoma a long-awaited therapy that has demonstrated a statistically significant reduction in the risk of disease recurrence or death by almost a third.”

“Keytruda is the first adjuvant therapy approved for certain patients with renal cell carcinoma in Europe, providing the option of immunotherapy earlier in the course of their treatment,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “This approval demonstrates our progress in bringing Keytruda to patients with earlier stages of cancer, with the goal of helping more patients around the globe prevent disease recurrence.”

This approval allows marketing of Keytruda monotherapy in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland.

Merck has a broad clinical development program exploring Keytruda, as monotherapy or in combination, as well as several other investigational and approved medicines across multiple settings and stages of RCC, including adjuvant and advanced or metastatic disease.
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The approval was based on data from KEYNOTE-564 (NCT03142334), a multicenter, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 994 patients with increased risk of recurrence of RCC defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). Patients must have undergone a partial or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion[s] in M1 NED participants) with negative surgical margins for at least four weeks prior to the time of screening. Patients with active autoimmune disease or a medical condition that required immunosuppression were excluded from the study. The primary efficacy outcome measure was investigator-assessed DFS. The secondary efficacy outcome measure was overall survival (OS). Patients with RCC with clear cell component were randomized (1:1) to receive Keytruda 200 mg administered intravenously every three weeks (n=496) or placebo (n=498) for up to one year until disease recurrence or unacceptable toxicity.

At a pre-specified interim analysis with a median follow-up time of 23.9 months, Keytruda demonstrated a statistically significant improvement in DFS, reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared with placebo in patients with RCC at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Updated efficacy results with a median follow-up time of 29.7 months demonstrated Keytruda reduced the risk of disease recurrence or death by 37% (HR=0.63 [95% CI, 0.50-0.80]; p<0.0001) compared with placebo. Median DFS has not been reached for either group. The trial will continue to assess OS as a secondary outcome measure.

The safety of Keytruda as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of RCC across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks) in clinical studies. In this patient population, the most frequent adverse reactions with Keytruda were fatigue (31%), diarrhea (22%) and nausea (21%). The majority of adverse reactions reported for Keytruda monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions. The incidences of immune-related adverse reactions were 36.1% for all Grades and 8.9% for Grades 3-5 for Keytruda monotherapy in the adjuvant setting (n=1,480) and 24.2% for all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). No new immune-related adverse reactions were identified in the adjuvant setting.

Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. 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 which may affect both tumour cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research programme. There are currently more than 1,700 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.