Merck's KEYTRUDA® Gains New Approvals in Japan for Specific NSCLC and Urothelial Carcinoma Patients

Merck, also known as MSD outside the United States and Canada, has announced that Japan's Ministry of Health, Labor and Welfare has approved new indications for its anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for certain types of lung and urothelial cancers.

The new approvals include:
1. **Non-Small Cell Lung Carcinoma (NSCLC):** KEYTRUDA, in combination with chemotherapy, is approved as a neoadjuvant treatment followed by monotherapy as an adjuvant treatment. This approval is based on the results from the Phase 3 KEYNOTE-671 trial, which showed that this combination significantly improved overall survival rates, reducing the risk of death by 28%.

2. **Radically Unresectable Urothelial Carcinoma:**
- **First-Line Treatment:** The combination of KEYTRUDA with Padcev (enfortumab vedotin-ejfv) for patients is approved based on findings from the Phase 3 KEYNOTE-A39 trial. This combination therapy significantly improved overall survival and progression-free survival rates, reducing the risk of death by 53%.
- **Monotherapy:** KEYTRUDA is also approved as a monotherapy for patients with this type of carcinoma who are not eligible for any platinum-containing chemotherapy, based on results from the Phase 2 KEYNOTE-052 trial.

Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories, highlighted the significance of these approvals in providing new treatment options for patients with resectable NSCLC and radically unresectable urothelial carcinoma in Japan.

### Detailed Trial Results

**NSCLC:**
- **KEYNOTE-671 Trial:** This study showed that patients treated with KEYTRUDA plus chemotherapy in the neoadjuvant setting followed by KEYTRUDA monotherapy after surgical resection had a 28% lower risk of death compared to those who received a placebo with chemotherapy. The median overall survival for the KEYTRUDA-treated group was not reached, while it was 52.4 months for those on the placebo regimen. Additionally, the KEYTRUDA-based regimen reduced the risk of disease recurrence, progression, or death by 42%.

**Urothelial Carcinoma:**
- **KEYNOTE-A39 Trial:** The first interim analysis of this study included 886 chemotherapy-naïve patients with radically unresectable urothelial carcinoma. Results showed that the combination of KEYTRUDA and enfortumab vedotin significantly reduced the risk of death by 53% and the risk of disease progression or death by 55% compared to the standard gemcitabine plus cisplatin or carboplatin treatment.
- **KEYNOTE-052 Trial:** For patients who are ineligible for platinum-containing chemotherapy, the trial demonstrated the effectiveness of KEYTRUDA monotherapy in treating radically unresectable urothelial carcinoma.

### Prevalence and Impact

Lung cancer remains the leading cause of cancer-related deaths worldwide, with approximately 2.4 million new cases and 1.8 million deaths in 2022. In Japan alone, there were around 130,000 new cases in 2019 and about 75,000 deaths in 2020. Non-small cell lung carcinoma accounts for about 85% of lung cancer cases.

Urothelial carcinoma, commonly known as bladder cancer, starts in the urothelial cells lining the urinary tract. Globally, around 614,300 new cases of bladder cancer are reported annually. In Japan, 25,000 new cases are diagnosed each year. In the U.S., around 83,190 new cases are expected in 2024, with approximately 12% being locally advanced or metastatic at diagnosis. Many patients diagnosed at an advanced stage face a poor prognosis.

### About KEYTRUDA

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that enhances the body’s immune response to detect and fight tumor cells. It 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 can affect both tumor and healthy cells.

### Conclusion

These new approvals of KEYTRUDA by the Japanese Ministry of Health, Labor and Welfare mark significant advancements in the treatment options available for patients with resectable non-small cell lung carcinoma and radically unresectable urothelial carcinoma, meeting critical unmet medical needs.