Merck’s KEYTRUDA® Receives Two New Approvals in Japan for Esophageal Squamous Cell Carcinoma and a Six-Week Dosing Regimen

Compiled by S.Li

Recently, MSD announced that its PD-1 antibody therapy Keytruda has received two latest approvals from the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan.

It is reported that the two latest approvals are specifically as follows: (1) monotherapy for the treatment of patients with PD-L1-positive, unresectable, advanced or recurrent esophageal squamous cell carcinoma (ESCC) after chemotherapy; (2) the additional recommended dosing regimen of Keytruda at 400 mg every six weeks (Q6W) has been approved, administered via intravenous infusion over more than 30 minutes, for all approved adult indications, including both Keytruda monotherapy and combination therapy.

Among them, the Keytruda 400 mg Q6W dosing regimen is a new dose option provided in addition to the current 200 mg every three weeks (Q3W) dose. To date, Keytruda has obtained 13 indications in Japan for seven types of tumors as well as MSI-H tumors.

The approval of Keytruda for the treatment of patients with ESCC is based on the results from the global Phase 3 clinical trial KEYNOTE-181. In this trial, Keytruda monotherapy improved overall survival (OS) in patients with PD-L1-positive (CPS ≥10) recurrent or metastatic ESCC compared with chemotherapy (paclitaxel, docetaxel, or irinotecan) (HR = 0.64 [95% CI, 0.46–0.90]). The median OS was 10.3 months (95% CI, 7.0–13.5) in the Keytruda group versus 6.7 months (95% CI, 4.8–8.6) in the chemotherapy group.The study met its primary overall survival (OS) endpoint, with Keytruda demonstrating an OS benefit and a favorable safety profile in patients with PD-L1–positive advanced esophageal cancer.

The approval of the six-week dosing regimen for Keytruda was based on pharmacokinetic modeling and exposure-response analysis. The pharmacokinetic modeling data were derived from the interim analysis results of KEYNOTE-555. In this trial, 100 patients were assigned to receive Keytruda 400 mg every six weeks (Q6W). An analysis was conducted on the first 44 patients with sufficient follow-up data to assess efficacy. The results showed an objective response rate (ORR) of 38.6% (n=17/44; 95% CI: 24.4–54.5), a complete response (CR) rate of 9.1% (n=4/44), and a partial response (PR) rate of 29.5% (n=13/44) in the six-week dosing group. These efficacy outcomes were comparable to those observed in previous melanoma trials evaluating Keytruda monotherapy. Additionally,The safety profile of Keytruda 400 mg Q6W is consistent with that of Keytruda 200 mg Q3W, which has been established in more than 12 tumor types.

Keytruda is a blockbuster anti-PD-1 therapy developed by MSD. It works by enhancing the human immune system’s ability to detect and combat tumor cells. As a humanized monoclonal antibody, Keytruda blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that can affect both tumor cells and healthy cells.

According to statistics, Keytruda has secured approval in the United States for more than 10 oncology indications, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck cancer, hepatocellular carcinoma, and renal cell carcinoma. In China (marketed as Keyruida), it has also been approved for the treatment of melanoma and non-small cell lung cancer. Its six-week dosing regimen has currently been approved in multiple regions, including the United States, Japan, and Europe.

Reference Source: Merck’s KEYTRUDA® (pembrolizumab) Receives Two New Approvals in Japan