FDA Approves MSD’s Keytruda Combinations with Padcev for Muscle-Invasive Bladder Cancer

The approvals expand the use of Keytruda and Keytruda Qlex alongside Padcev into the perioperative treatment setting for adults with muscle-invasive bladder cancer, regardless of cisplatin eligibility.

The US Food and Drug Administration (FDA) has approved two new combinations from Merck & Co. (MSD) for the treatment of adults with muscle-invasive bladder cancer (MIBC), expanding the role of its immunotherapy platform Keytruda (pembrolizumab).

The approvals cover:

• Keytruda (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv)

• Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) plus Padcev
  

Both combinations are approved for use in the neoadjuvant setting before surgery and adjuvant setting after surgery for patients with MIBC, including those who are not eligible for cisplatin-based chemotherapy.

The FDA decision was supported by results from the Phase III KEYNOTE-B15 trial, also known as EV-304, which evaluated pembrolizumab and enfortumab vedotin-ejfv compared with standard neoadjuvant chemotherapy followed by surgery.

The approval further strengthens MSD’s oncology portfolio, with Keytruda already one of the most widely used cancer immunotherapies globally.

Phase III KEYNOTE-B15 Trial Shows Reduced Risk of Disease Events

The KEYNOTE-B15 study enrolled 808 patients with muscle-invasive bladder cancer and assessed whether the combination of pembrolizumab and enfortumab vedotin-ejfv could improve outcomes compared with chemotherapy followed by surgery.

In patients eligible for cisplatin-based chemotherapy, the Keytruda and Padcev combination demonstrated a:

• 47% reduction in the risk of event-free survival (EFS) events

• 35% reduction in the risk of death
  

Median event-free survival was not reached among patients receiving pembrolizumab plus enfortumab vedotin-ejfv.

The combination also improved pathological complete response rates, meaning no detectable cancer remained in tissue samples following treatment.

Patients receiving the MSD combination achieved:

• 55.8% pathological complete response rate
  

compared with:

• 32.5% for chemotherapy plus surgery
  

These results suggest that combining immune checkpoint inhibition with antibody-drug conjugate therapy could provide a more effective treatment approach for some patients with MIBC.

Expanding Treatment Options Before and After Surgery

Muscle-invasive bladder cancer represents an aggressive form of bladder cancer where tumours have grown into the muscle layer of the bladder wall.

Standard treatment has traditionally involved chemotherapy followed by radical cystectomy, a surgical procedure to remove the bladder.

However, a significant proportion of patients are unable to receive cisplatin-based chemotherapy due to factors including kidney function, age or other health conditions.

The latest FDA approvals expand treatment options by providing a perioperative approach that can be used regardless of cisplatin eligibility.

MSD Research Laboratories senior vice-president and global clinical development oncology head Dr Marjorie Green said the approvals represent progress for patients with MIBC.

“The results from KEYNOTE-B15, together with KEYNOTE-905, highlight the potential of these new treatment options for patients regardless of cisplatin eligibility in the perioperative setting and mark a promising step forward in the treatment of muscle-invasive bladder cancer,” Green said.

Safety Profile of Keytruda and Padcev Combination

The FDA approval included safety data from patients treated in the neoadjuvant setting.

Permanent discontinuation of pembrolizumab due to adverse reactions occurred in:

• 17% of patients during the neoadjuvant phase
  

Reported serious adverse reactions included:

• Rash

• Pneumonitis or interstitial lung disease

• Diarrhoea
  

Fatal adverse reactions occurred in:

• 1.7% of patients during the neoadjuvant phase

• 3.2% of patients during the adjuvant phase
  

Healthcare providers will continue to monitor patients receiving the combination for immune-related adverse events and complications associated with treatment.

Keytruda and Padcev Continue to Expand Across Bladder Cancer

The latest approval builds on previous regulatory decisions supporting the use of Keytruda-based combinations in bladder cancer.

The FDA decision follows earlier approval activity linked to the Phase III KEYNOTE-905 (EV-303) trial, which also evaluated pembrolizumab and enfortumab vedotin-ejfv in patients with MIBC.

Outside the US, the European Commission recently approved MSD’s Keytruda combination with Padcev as a neoadjuvant treatment option for MIBC.

The continued expansion of the Keytruda platform highlights the growing importance of combination approaches in oncology, particularly therapies that pair immune checkpoint inhibitors with targeted cancer treatments such as antibody-drug conjugates.

What This Means for the Muscle-Invasive Bladder Cancer Market

The FDA approvals mark a significant development in the treatment landscape for muscle-invasive bladder cancer by introducing a new perioperative option that could reduce reliance on traditional chemotherapy pathways.

For oncologists, the decision provides another treatment strategy for managing MIBC patients before and after surgery.

For the pharmaceutical market, the approval reinforces MSD’s position in immuno-oncology while highlighting the increasing role of combination therapies in improving cancer outcomes.

As clinical data continues to mature, the long-term impact of Keytruda and Padcev combinations will depend on durability of response, overall survival benefits and adoption across treatment centres.

Summary

The FDA has approved MSD’s Keytruda and Keytruda Qlex combinations with Padcev for adults with muscle-invasive bladder cancer.

The approvals are based on Phase III KEYNOTE-B15 data showing:

• A 47% reduction in event-free survival risk

• A 35% reduction in risk of death

• Higher pathological complete response rates compared with chemotherapy
  

The decision expands treatment options for patients with MIBC regardless of cisplatin eligibility and represents another step forward for combination immunotherapy approaches in oncology.

---

Discover how nuaxia can support your next medical education initiative:

• Find out more about our specialist services - Moore's Outcome Assessments, Educational Needs Assessments and Patient Impact Studies for the Medical Education sector 

• Contact us on: support@nuaxia.com