Investigational Anti-PD-1 Agent Shows Potential for Treatment of Unresectable or Metastatic MSI-H/dMMR Solid Tumors

In patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient (MSI-H/dMMR) solid tumors that fail to respond to the standard therapy, the novel anti-PD-1 inhibitor, HLX10, has demonstrated positive efficacy and safety outcomes in a phase 2 clinical trial (NCT03941574), according to a press release issued by Shanghai Henlius Biotech, Inc.

The primary outcome of the study is the objective response rate (ORR). Secondary endpoints include 6-month overall survival (OS), 6-month progression-free survival (PFS), and duration of response (DOR).

The single-arm study has an estimated enrollment of 60 participants with an estimated completion date of April 30, 2021. In order to participate, patients must be between 18 and 75 years old. Additionally, they must have unresectable or metastatic MSI-H or dMMR malignant solid tumors. Tumors must have disease progression or intolerable reactions to previous anti-cancer treatment. Patients who have undergone previous organ or bone marrow transplantation are not eligible. Additionally, patients with uncontrolled pleural effusion, pericardial effusion, or ascites after appropriate intervention measures.

The agent has been approved for clinical trials and study in the United States, China, the European Union and others, and is currently being evaluated in 10 clinical trials. Additionally, 10 products and 8 combination therapies are currently being evaluated in clinical studies. HLX10 being investigated for efficacy in a wide range of tumors, including lung cancer, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, and gastric cancer. Additionally, the PD-1 is involved in 3 phase 3 global multi-center clinical trials in squamous non-small cell lung cancer, extensive-stage small cell lung cancer, and neo-/adjuvant treatment for gastric cancer.

MSI-H is caused by the defect of mismatch repair that can potentially lead to base mismatch or insert in microsatellites during DNA replication. The acclamation of these bases causes microsatellite instability. MSI-H has a prevalence of 14% across all tumor types. Patients with this disease tend to have a higher response rate to immune checkpoint inhibitors, making it an important biomarker for making immunotherapy predictions in patients with solid tumors. MSI-H occurs most often in endometrial cancer, colorectal cancer, gastric cancer, renal cell carcinoma, and ovarian cancer.

Results of the study will be presented at upcoming medical conferences, and Shanghai Henlius Biotech, Inc also plans to submit a new drug application to China’s National Drug Products Administration.

_REFERENCE:

_{Henlius plans to file the NDA of novel anti-PD-1 mAb HLX10 for the treatment of MSI-H solid tumors, the Phase 2 Clinical Trial has Met the Primary Endpoint News Release. 3/28/2021. March 26, 2021. Accessed March 29, 2021. https://bit.ly/3w5ahzn}