Merck Secures CHMP Support for KEYTRUDA® Plus Padcev® in Muscle-Invasive Bladder Cancer
Merck, known as MSD outside the United States and Canada, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of KEYTRUDA in combination with Padcev for adults with resectable muscle-invasive bladder cancer (MIBC) who are not eligible for cisplatin-containing chemotherapy.
The recommendation covers the use of KEYTRUDA and Padcev as neoadjuvant therapy before surgery, followed by continued treatment with the regimen after radical cystectomy as adjuvant therapy. The recommendation also includes KEYTRUDA SC, known in the United States as KEYTRUDA QLEX.
The CHMP opinion now moves to the European Commission for final review and potential marketing authorization across the European Union, as well as Iceland, Liechtenstein, and Norway. A final regulatory decision is expected during the third quarter of 2026.
The recommendation could mark a significant advancement for patients with muscle-invasive bladder cancer who are unable to receive cisplatin-based chemotherapy, which is currently considered a standard treatment option for many bladder cancer patients. Individuals who are not eligible for cisplatin therapy often have limited alternatives and face a high risk of cancer recurrence even after surgery.
Muscle-invasive bladder cancer is an aggressive disease in which cancer cells spread into the muscular wall of the bladder. Although surgery can remove visible tumors, many patients remain at risk of relapse due to microscopic disease that may persist after treatment. Researchers and clinicians have increasingly focused on developing perioperative treatment approaches that can improve long-term outcomes both before and after surgery.
According to Merck, the CHMP’s positive recommendation is based on results from the Phase 3 KEYNOTE-905 trial, also referred to as EV-303, which was conducted in collaboration with Pfizer and Astellas Pharma.
The clinical study evaluated KEYTRUDA plus Padcev as a perioperative treatment regimen compared with surgery alone in patients with muscle-invasive bladder cancer who were either ineligible for or declined cisplatin-based chemotherapy.
The trial produced statistically significant and clinically meaningful improvements across several important treatment endpoints, including event-free survival, overall survival, and pathologic complete response rates.
One of the most notable findings from the study was the substantial reduction in the risk of disease-related events. Patients treated with KEYTRUDA plus Padcev experienced a 60% reduction in the risk of event-free survival events compared with patients who underwent surgery alone.
Median event-free survival was not reached in the treatment arm at the time of analysis, demonstrating prolonged disease control among patients receiving the combination therapy. By comparison, patients treated with surgery alone had a median event-free survival of 15.7 months.
The regimen also demonstrated a major improvement in overall survival outcomes. According to trial data, KEYTRUDA plus Padcev reduced the risk of death by 50% compared with surgery alone.
Median overall survival was not reached for patients receiving the combination regimen, while patients treated with surgery alone had a median overall survival of 41.7 months.
Researchers additionally observed a dramatic improvement in pathologic complete response rates, which refers to the absence of detectable cancer in tissue samples following treatment and surgery. Patients receiving KEYTRUDA plus Padcev achieved a pathologic complete response rate of 57.1%, compared with only 8.6% among patients treated with surgery alone.
These findings have generated significant interest within the oncology community because achieving a pathologic complete response is often associated with improved long-term clinical outcomes for cancer patients.
“Patients in Europe with resectable muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy have limited treatment options and are at high risk for disease recurrence,” said Marjorie Green.
Dr. Green explained that the positive CHMP recommendation moves the company closer to potentially offering a new treatment strategy that addresses an important unmet need in bladder cancer care. She noted that the KEYTRUDA-based regimen has the potential to provide patients with treatment both before and after surgery based on the compelling results observed in the KEYNOTE-905 trial.
The results from the trial were first presented during a Presidential Symposium session at the ESMO Congress 2025 and were later published in The New England Journal of Medicine, further highlighting the significance of the findings within the medical community.
The regulatory progress in Europe follows an earlier approval in the United States. In November 2025, the U.S. Food and Drug Administration approved KEYTRUDA and KEYTRUDA QLEX in combination with Padcev as neoadjuvant treatment followed by adjuvant therapy after cystectomy for adult patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy.
That FDA approval represented an important milestone in expanding treatment options for bladder cancer patients who previously had few alternatives outside surgery alone.
KEYTRUDA, Merck’s anti-PD-1 therapy, has become one of the most widely used immunotherapies across multiple cancer types. Padcev, an antibody-drug conjugate targeting Nectin-4, has also demonstrated strong clinical activity in urothelial cancers. Together, the therapies are designed to combine immune system activation with targeted cancer cell destruction.
If formally approved by the European Commission later this year, the combination could establish a new perioperative treatment approach for cisplatin-ineligible muscle-invasive bladder cancer patients across Europe. Healthcare providers and researchers believe the regimen may help reduce recurrence risk, extend survival, and improve outcomes for patients facing an aggressive form of bladder cancer with historically limited treatment choices.
About bladder cancer
In 2022, bladder cancer changed the lives of more than 600,000 people around the world. In Europe, it is estimated there were approximately 224,700 patients diagnosed with bladder cancer and more than 70,300 deaths from the disease in 2022. According to some clinical practice guidelines, about 25% of newly diagnosed bladder cancer cases are MIBC. The standard of care for patients with MIBC has been neoadjuvant cisplatin-based chemotherapy followed by surgery, which is shown to prolong survival. However, up to half of patients with MIBC are not eligible to receive cisplatin and face limited treatment options, typically undergoing surgery alone.
About Merck’s research in genitourinary cancers
Merck is advancing research aimed at helping transform the treatment landscape and broaden options for people with genitourinary (GU) cancers, including bladder, kidney and prostate cancers. Globally, GU cancers account for an estimated 2.6 million new cancer diagnoses each year, equaling over 1 in 8 of all cancer incidences. Through a robust clinical development program with more than 50 ongoing clinical trials evaluating more than 22,000 patients around the world, Merck is investigating the potential of several portfolio medicines and pipeline assets, leveraging multiple novel combination strategies, across various stages of disease, to help address unmet needs in GU cancers.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 100 mg
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 tumor 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 tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 2,800 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.
About KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous use
KEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA QLEX is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).
