On October 10, Merck announced that its PD-1 inhibitor Keytruda (Pembrolizumab, trade name Correda) has been approved by China's National Food and Drug Administration (NMPA) as a single agent for the treatment of hepatocellular carcinoma (HCC) patients who have previously received sorafenib or oxaliplatin-containing chemotherapy. So far, Keytruda has been approved for 9 indications in China.
Keytruda, a PD-1 inhibitor developed by Merck, blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that may affect tumor cells and healthy cells, thereby enhancing the body's immune system's ability to detect and destroy cancer cells.
This new indication for liver cancer is based on data from the Phase III KEYNOTE-394 trial, which was designed to evaluate Keytruda plus optimal supportive therapy as compared with placebo plus optimal supportive therapy in previously treated Asian patients with advanced hepatocellular carcinoma. The primary end point of the trial was overall survival (OS), and secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response, and disease control rate.
The results showed that the trial group reduced the risk of death by 21 percent compared with the placebo group. The median OS was 14.6 months in the trial group and 13.0 months in the placebo group. In addition, the combination treatment reduced the risk of disease progression or death by 26 percent. ORR was 12.7% in the trial group and 1.3% in the placebo group. With regard to safety, treatment-related adverse events (TRAE) occurred in 66.9% of patients in the trial group and 49.7% of patients in the placebo group, and grade 3-5 TRAE occurred in 14.4% of patients in the trial group and 5.9% of patients in the placebo group.
Keytruda was first approved for advanced melanoma in the United States in September 2014, becoming the first PD-1 inhibitor approved by the FDA. The drug has now been approved for more than 30 indications in the United States. In July 2018, Keytruda was approved for the treatment of melanoma for the first time in China. Excluding this new indication, Keytruda has been approved for 8 indications in China:
● Unresectable or metastatic melanoma that has failed first-line treatment;
● Pemetrexed combined with platinum-based chemotherapy for first-line treatment of epidermal growth factor receptor (EGFR) -negative and anaplastic lymphoma kinase (ALK) -negative metastatic non-squamous non-small cell lung cancer (NSCLC);
● First-line monotherapy for locally advanced or metastatic NSCLC with EGFR mutation-negative and ALK-negative tumors assessed as PD-L1 tumor fraction (TPS) ≥1% by NMPA approved assays;
● Combination of carboplatin and paclitaxel as first-line therapy for patients with metastatic squamous NSCLC;
● Monotherapy for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma whose tumors express PD-L1 (combined positive score (CPS) ≥10) assessed by an NMPA approved assay, who have failed previous first-line systemic therapy;
● Combined platinum and fluorouracil chemotherapy drugs for the first-line treatment of locally advanced unresectable or metastatic esophageal or gastroesophageal junction cancer;
● Single-agent use as first-line therapy in patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma whose tumors express PD-L1[CPS≥20] as assessed by well-validated assays;
● Single agent is used as first-line treatment for patients with wild-type, unresectable or metastatic high microsatellite instability (MSI-H) or mismatch repair defective (dMMR) colorectal cancer with KRAS, NRAS, and BRAF genes.
Dr. Li Zhengqing, Senior Vice President of MSD China Research and Development Center, said:
Keykey-394 was released at a global academic conference earlier this year, and now Keytruda has been approved in China as a second-line treatment for advanced hepatocellular carcinoma. As investigators, we are very excited. At present, the survival benefit of patients with advanced hepatocellular carcinoma after treatment is low, and there is still a huge medical need to be met. The approval of the new Keytruda indication provides a new weapon in the fight against hepatocellular carcinoma, a refractory cancer, and a new treatment option for clinicians and patients.
Keytruda generated $17.2 billion in global sales last year and $10.061 billion in revenue in the first half of this year, up nearly 30% from a year earlier.
References:
1. Treatment of hepatocellular carcinoma! Merck's blockbuster PD-1 inhibitor was approved for the 9th indication in China; Medical mission hills
2. Merck PD-1 inhibitor Corida ® was approved as a new indication for HCC treatment in China, for patients with hepatocellular carcinoma (HCC) who had received sorafenib or oxaliplatin chemotherapy previously; MSD China
