Merck’s Keytruda Gets Japanese Approvals for Certain Patients With NSCLC And Urothelial Carcinoma

Merck’s Keytruda gets new approvals in Japan for certain patients with NSCLC and radically unresectable urothelial carcinoma

Overview

Merck, known as MSD outside of the United States and Canada, announced that the Japanese Ministry of Health, Labor and Welfare (MHLW) has approved new indications for Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in certain lung and urothelial cancers.

About Approval

• In lung and urothelial cancers: Keytruda in combination with chemotherapy as a neoadjuvant treatment, then continued as monotherapy as an adjuvant treatment.
• for patients with non-small cell lung carcinoma (NSCLC) based on results from the phase 3 KEYNOTE-671 trial.
• Keytruda in combination with Padcev (enfortumab vedotin-ejfv) for the first-line treatment of patients with radically unresectable urothelial carcinoma based on results from the phase 3 KEYNOTE-A39 trial (also known as EV-302), which was conducted in a research collaboration with Pfizer (previously Seagen) and Astellas.
• Keytruda monotherapy in patients with radically unresectable urothelial carcinoma who are not eligible for any platinum-containing chemotherapy based on results from the phase 2 KEYNOTE-052 trial.

From the Merck Research Laboratories

• For certain patients in Japan who are diagnosed with resectable non-small cell lung carcinoma and radically unresectable urothelial carcinoma, there is a need for new, effective treatment options,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. 
• With these new approvals, we look forward to providing Keytruda as monotherapy and in combination with other treatment regimens as we aim to address the unmet needs of these patients.

Behind the approval: KEYNOTE-671 trial

• •he approval of Keytruda in combination with chemotherapy as a neoadjuvant treatment, then continued as monotherapy as an adjuvant treatment for patients with NSCLC is based on results from the phase 3 KEYNOTE-671 trial. 
• In this study, Keytruda plus chemotherapy in the neoadjuvant setting followed by Keytruda as monotherapy after surgical resection significantly improved overall survival (OS), reducing the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; one-sided p=0.00517) in patients with stage II, IIIA or IIIB NSCLC, regardless of PD-L1 expression, versus placebo plus chemotherapy in the neoadjuvant setting followed by placebo after surgical resection at a median follow-up of 29.8 months (range, 0.4 to 62.0 months). 
• For patients who received the Keytruda-based regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. 
• The Keytruda-based regimen also improved event-free survival, reducing the risk of disease recurrence, progression or death by 42% (HR=0.58 [95% CI, 0.46-0.72]; p<0.00001) compared to the chemotherapy-placebo regimen.

About Lung cancer in Japan

• Lung cancer is the leading cause of cancer death worldwide. 
• In 2022, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. 
• In Japan alone, there were approximately 130,000 new cases of lung cancer diagnosed in 2019 and about 75,000 deaths from the disease in 2020. 
• The overall five-year survival rate for lung cancer patients in Japan is about 35%. 
• Non-small cell carcinoma is the most common type of lung cancer, accounting for about 85% of all cases. 
• Non-small cell lung carcinoma is more common, whereas small cell lung cancer is less common and typically grows more quickly.

Approval of Keytruda+ enfortumab vedotin (phase 3 KEYNOTE-A39 trial)

• The approval of Keytruda in combination with enfortumab vedotin for the first-line treatment of patients with radically unresectable urothelial carcinoma is based on results from the first interim analysis of the phase 3 KEYNOTE-A39 trial. 
• It evaluated the combination compared to gemcitabine plus cisplatin or carboplatin in 886 chemotherapy-naïve patients with radically unresectable urothelial carcinoma. 
• In this study, the Keytruda plus enfortumab vedotin combination significantly improved OS and progression-free survival (PFS), reducing the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.00001) and also reducing the risk of disease progression or death by 55% (HR=0.45 [95% CI, 0.38-0.54]; p<0.00001) versus gemcitabine plus cisplatin or carboplatin.

Approval of Keytruda (phase 2 KEYNOTE-052 trial)

• The approval of Keytruda as monotherapy for patients with radically unresectable urothelial carcinoma who are not eligible for any platinum-containing chemotherapy is based on results from the phase 2 KEYNOTE-052 trial.
• It evaluated Keytruda monotherapy compared to chemotherapy alone in 370 chemotherapy-naïve patients with radically unresectable urothelial carcinoma who were not eligible for any platinum-containing chemotherapy.

Urothelial carcinoma in Japan 

• Urothelial carcinoma, a type of bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis and some other organs. 
• Globally, it is estimated that approximately 614,300 new cases of bladder cancer are reported annually. 
• In Japan, 25,000 people are estimated to be diagnosed with bladder cancer each year, and in the US, it is estimated that approximately 83,190 people will be diagnosed with bladder cancer in 2024. 
• Of those patients diagnosed in the US, approximately 12% of cases are locally advanced or metastatic urothelial carcinoma at diagnosis, and many patients who are diagnosed at an advanced stage face a poor prognosis.

The PD-1 therapy: Keytruda

• 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 tumour cells and healthy cells.

Immuno-oncology clinical research program by Merck

• Merck has the industry’s largest immuno-oncology clinical research program. 
• There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. 
• The Keytruda clinical programme 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.

The Clinical Collaboration

• Astellas and Seagen entered a clinical collaboration agreement with Merck to evaluate the combination of Astellas’ and Seagen’s Padcev (enfortumab vedotin-ejfv) and Merck’s Keytruda (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. 
• Padcev and the Padcev device are trademarks jointly owned by Agensys, Inc., and Seagen Inc.
• Pfizer Inc. completed its acquisition of Seagen on December 14, 2023.

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