On October 10, Merck announced that its PD-1 inhibitor, Keytruda (aborizumab, trade name Creida), has been approved by the Chinese State Food and Drug Administration (NMPA) for monotherapy in patients with hepatocellular carcinoma (HCC) who had previously received sorafenib or oxaliplatin-containing chemotherapy. So far, there are nine approved indications for Keytruda 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, and subsequently enhancing the ability of the human immune system to detect and eliminate cancer cells.
The approved new indication for liver cancer is based on data from the phase III clinical trial, KEYNOTE-394, designed to evaluate the efficacy of Keytruda combined with best supportive care versus placebo combined with best supportive care in Asian, previously treated patients with advanced hepatocellular carcinoma. The primary study endpoint of the trial is overall survival (OS), and the secondary study endpoints include progression-free survival (PFS), objective response rate (ORR), sustained remission duration, and disease control rate.
The results showed that the trial group reduced the death risk by 21% compared to the placebo group. The median OS was 14.6 months, compared to 13.0 months in the placebo group. In addition, combination therapy reduces the risk of disease progression or death by 26%. The ORR was 12.7% in the trial group and 1.3% in the placebo group. In terms of safety, treatment-related adverse events (TRAE) occurred in 66.9% of patients and 49.7% of patients in placebo group, and grade 3 – 5 occurred in 14.4% of trial group and 5.9% of placebo group with TRAE.
In September 2014, Keytruda was first approved in the United States in treating advanced melanoma, becoming the first FDA-approved PD-1 inhibitor, and it has now been approved for more than 30 indications in the United States. In July 2018, Keytruda was first approved for melanoma treatment in China. Excluding this new indication, the eight indications approved by Keytruda in China were:
●: unresectable or metastatic melanoma with failed first-line treatment;
● in combination with pemetrexed and platinum chemotherapy is used for the first-line treatment of metastatic non-squamous non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK) -negative conditions;
The ● was evaluated by the NMPA-approved tests as a PD-L1 tumor proportion fraction (TPS) of 1% EGFR gene mutation-negative and ALK-negative local advanced or metastatic NSCLC first-line monotherapy;
Combine carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous NSCLC;
● monotherapy was used by NMPA-approved tests to evaluate the treatment of patients with tumors expressing PD-L1 [composite positive score (CPS) 10], previous first-line systemic therapy failure, locally advanced or metastatic esophageal squamous cell carcinoma.
●, combined with platinum and fluorouracil chemotherapeutics, is used for the first-line treatment of patients with locally advanced unresectable or metastatic esophageal or gastroesophageal junction cancer;
● monotherapy was used to evaluate the first-line treatment of patients with metastatic or unresectable recurrent head and NS cell carcinoma with tumor expressing PD-L1 [CPS 20] by well-validated testing;
The ● monotherapy is used for the first-line treatment of patients with KRAS, NRAS, and BRAF genes that are all wild-type, unresectable or metastatic high microsatellite instability (MSI-H), or mismatch repair gene-deficient (dMMR) colorectal cancer.
Dr. Li Zhengqing, Senior Vice President, President of China R & D Center, Merck, said:
The KEYNOTE-394 study, which was released at a global academic conference earlier this year, is now encouraged to approve the Keytruda second-line treatment for advanced hepatocellular carcinoma in China. At present, the post-treatment survival benefit of patients with advanced HCC is low, and there are still huge medical needs to be met. The approval of the new Keytruda certificate provides a new 'weapon' against the refractory type of hepatocellular carcinoma, and also provides new treatment options for clinicians and patients.
Keytruda's global sales reached $17.2 billion last year, and it generated $10.061 billion in revenue in the first half of this year, up nearly 30% from a year earlier.
