Merck's KEYTRUDA® (pembrolizumab) Approved in China in Combination with Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Esophageal and GEJ Carcinoma

September 7, 2021 /BioonBIOON/ --MSD (Merck & Co.) recently announced that China's National Medical Products Administration (NMPA) has approvedAnti-PD-1 therapy Keytruda (Keruida, generic name: pembrolizumab, pabolizumab), in combination with chemotherapy (platinum + fluoropyrimidine), for the first-line treatment of patients with locally advanced unresectable or metastatic esophageal or gastroesophageal junction (GEJ) adenocarcinoma.。To date,Keytruda has been approved in China for 8 indications across 5 different cancers.。

It is worth noting that,Keytruda is the first anti-PD-1 therapy approved in China for the first-line treatment of advanced esophageal or gastroesophageal junction (GEJ) cancer, regardless of histology or PD-L1 expression.This approval will change the current first-line treatment paradigm for this patient population.In the pivotal Phase 3 KEYNOTE-590 trial,Regardless of histology or PD-L1 expression status, Keytruda plus chemotherapy significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with chemotherapy.

In March this year, Keytruda + chemotherapy (platinum + fluoropyrimidine) received USFDAApproved for the first-line treatment of patients with metastatic or locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma who are not candidates for surgical resection or definitive radiotherapy. In China, Keytruda was previously approved as a monotherapy for second-line treatment.TumorPatients with PD-L1-expressing (CPS ≥ 10) recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Currently, through its extensive clinical program, MSD continues to investigate the therapeutic potential of Keytruda across multiple settings and stages of gastrointestinal cancers, including gastric cancer, hepatobiliary cancers, esophageal cancer, pancreatic cancer, colorectal cancer, and anal canal cancer, among others.

Dr. Scot Ebbinghaus, Vice President of Clinical Research at MSD Research Laboratories, said: “In China, esophageal cancer and gastroesophageal junction cancer are leading causes of death, and there has been limited progress in treatment for patients over the past few decades. Keytruda plus chemotherapy is the first approved anti-PD-1 regimen for first-line treatment. Now, we are able to provide patients with an immunotherapy option early in their treatment that has been proven to significantly improve survival.”

Results for the Overall Study Population in the KEYNOTE-590 Trial

This approval is based on data from the pivotal Phase 3 KEYNOTE-590 trial (NCT03189719). The trial evaluated KEYTRUDA in combination with chemotherapy (cisplatin plus 5-fluorouracil [5-FU]) as first-line treatment for patients with locally advanced unresectable or metastatic esophageal and gastroesophageal junction (GEJ) cancer.

Data show that in the overall study population (intention-to-treat [ITT] population), regardless of histology or PD-L1 expression status, compared with chemotherapy, Keytruda + chemotherapy: (1) significantly prolonged overall survival (median OS: 12.4 months vs. 9.8 months) and reduced the risk of death by 27% (HR=0.73; 95% CI: 0.62–0.86; p < 0.0001); (2) significantly prolonged progression-free survival (median PFS: 6.3 months vs. 5.8 months) and reduced the risk of disease progression or death by 35% (HR=0.65; 95% CI: 0.55–0.76; p < 0.0001); and (3) significantly improved the objective response rate (ORR: 45.0% vs. 29.3%) and prolonged the duration of response (median DOR: 8.3 months vs. 6.0 months).

InTumorIn a prespecified analysis of patients with PD-L1 expression (CPS ≥10) (n=383/749), compared with chemotherapy, Keytruda + chemotherapy: (1) significantly prolonged overall survival (median OS: 13.5 months vs 9.4 months) and reduced the risk of death by 38% (HR=0.62; 95% CI: 0.49-0.78; p<0.0001); (2) significantly prolonged progression-free survival (median PFS: 7.5 months vs 5.5 months) and reduced the risk of disease progression or death by 49% (HR=0.51; 95% CI: 0.41-0.65; p<0.0001); (3) significantly improved the objective response rate (ORR: 51.1% vs 26.9%) and prolonged the duration of response (median DOR: 10.4 months vs 5.6 months). In this study, the safety profile of Keytruda was consistent with that reported in previous studies.

The Chinese package insert for Keytruda indicates that the KEYNOTE-590 study evaluated the safety of Keytruda plus chemotherapy in 51 Chinese patients with esophageal cancer. The safety profile in Chinese patients was generally consistent with the known safety profiles of Keytruda monotherapy and chemotherapy.

Esophageal cancer is an aggressive, devastating malignancy with a high mortality rate, with few treatment options other than chemotherapy. For newDiagnosis, previously untreated patients urgently require therapeutic advances. Based on the results of the KEYNOTE-590 trial,Keytruda is the first anti-PD-1 therapy in combination with chemotherapy for the first-line treatment of esophageal cancer to demonstrate superior OS, PFS, and ORR compared with current standard-of-care chemotherapy, regardless of# TumorWhat is the histology or PD-L1 expression status.

Esophageal cancer is a particularly difficult-to-treat malignancy that originates in the inner lining (mucosa) of the esophagus and grows outward. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Globally, esophageal cancer is the seventh most commonDiagnosis...of cancer, and the sixth leading cause of cancer-related deaths. It is estimated that in 2018, there were over 572,000 new cases of esophageal cancer worldwide, with nearly 509,000 deaths. In China, esophageal cancer is the fifth most common cancer and the fourth leading cause of cancer mortality, with 90% of esophageal cancers being squamous cell carcinoma.

Keytruda is classified as a PD-(L)1 tumor immunotherapy that enhances the human immune system's ability to help detect and combat 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 immune responses that may affectTumorT lymphocytes of cells and healthy cells.

As of now, globally,Over 10 PD-(L)1 inhibitors are already availableTumorImmunotherapy Gains Market Approval, Keytruda Leads the Field, approved for multiple therapeutic indications, with global sales reaching USD 14.38 billion in 2020, representing a 30% year-on-year increase.

MSD has the largest immuno-oncology clinical development program in the industry, currently with over 1,500Clinical TrialCurrently investigating Keytruda in multiple types ofTumorand its role in the treatment context. The Keytruda clinical program is designed to understand the drug's role in cancer and factors that may predict patient benefit from Keytruda treatment, including exploring several differentBiomarker.(Bioon.com)

Original Source:Merck’s KEYTRUDA® (pembrolizumab) Approved in China in Combination With Chemotherapy for First-Line Treatment of Patients With Locally Advanced Unresectable or Metastatic Esophageal or Gastroesophageal Junction (GEJ) Carcinoma