How SHR-1210 works
SHR-1210 is a monoclonal antibody directed against programmed cell death 1 (PD-1), a protein found on the surface of specialized immune system cells called T-cells. When bound to its ligand, the programmed cell death ligand 1 (PD-L1), PD-1 suppresses the immune function of T-cells to ensure that they do not mistakenly attack healthy cells.
In several types of cancers, tumor cells evade immune attack by overexpressing PD-L1 on their surface. SHR-1210 works to block PD-1 and prevent it from binding to its ligand PD-L1. By doing so, SHR-1210 is designed to activate T-cells and restore their protective role, promoting immune attacks against cancer cells.
SHR-1210 in clinical trials
An open-label, single center, non-randomized and dose-escalation Phase 1 study (NCT02742935) was designed to evaluate the safety and tolerability of SHR-1210 in patients with advanced solid tumors (breast cancer, gastrointestinal cancer, lung cancer, nasopharynx cancer, colorectal carcinoma, and bladder cancer) who have failed current standard anti-tumor therapies. The study enrolled 58 patients who received ascending doses of SHR-1210 (60 mg, 200 mg, and 400 mg) once every two weeks.
Results showed that SHR-1210 was safe and well-tolerated, and also demonstrated promising antitumor activity, with an objective response rate of 31 percent and disease control rate of 46.5 percent.
Another open-label, multicenter, non-randomized and dose-escalation Phase 1 study (NCT02492789) is currently recruiting patients with advanced solid tumors across Australia to evaluate the safety and tolerability of SHR-1210. The study consists of two parts, a dose-escalation part, and an expansion part. In Part 1, SHR-1210 is injected into the bloodstream of patients at ascending dose levels of 1, 3, 6, and 10 mg/kg. In Part 2, additional patients are to be given fixed doses of SHR-1210 every four weeks.
Preliminary data from 23 patients showed that SHR1-210 treatment was safe although associated with a buildup of blood vessels in the skin (skin hemangioma). The recommended dose was found to be 200 mg every four weeks. The study is expected to be completed by 2018.
Esophageal squamous cell carcinoma (ESCC)
An open-label, single center, non-randomized and single-arm exploratory study (NCT03222440) aims to evaluate the safety and efficacy of radiation therapy combined with SHR-1210 in patients with locally advanced ESCC. The study is currently recruiting patients at the Tianjin Medical University Cancer Hospital in China and is expected to be completed by 2020.
SHR-1210 is also being studied in esophageal cancer in other clinical studies, including NCT03099382, NCT03187314, NCT03187314, and NCT03200691. All four trials are currently recruiting participants in China.
Hepatocellular carcinoma (HCC)
A randomized, multicenter Phase 2/3 study (NCT02989922) aims to evaluate the safety and efficacy of SHR-1210 in patients with advanced HCC whose cancer progressed with or who cannot tolerate systemic treatment. The study is currently recruiting patients across China and is expected to finish in 2019.
SHR-1210 is also being currently studied in China in cancers such as melanoma (NCT02738489), Hodgkin lymphoma (NCT03250962), non-small cell lung cancer (NCT03083041, NCT03085069, NCT03134872), and B-cell lymphoma (NCT03346642).
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