Patients with certain kinds of relapsed or refractory multiple myelomas can enroll in a clinical trial assessing a combination of NY-ESO SPEAR T-cells and Keytruda (pembrolizumab), according to the T-cell treatment’s developer, Adaptimmune Therapeutics.
To qualify for the study, patients’ tumor cells must express the NY-ESO or LAGE-1 proteins, or both. Expression is the process by which information from a gene is used to create a functional product like a protein.
This is the third clinical trial Adaptimune has started in a month. The company is also evaluating its AFP SPEAR T-cell therapy in hepatocellular carcinoma, the most common type of liver cancer, and its MAGE-A4 SPEAR T-cells in seven malignant solid tumors.
“We are excited to initiate this study as we have already seen encouraging data in a previous single-agent study of NY‑ESO SPEAR T-cells in patients with advanced myeloma in the context of stem cell transplantation,” Rafael Amado, Adaptimmune’s chief medical officer, said in a press release.
Keytruda, which targets the PD-1 protein associated with some cancers, has shown promise against multiple myeloma in combination with other therapies. There is preclinical-trial evidence “to support the view that the combination of NY-ESO SPEAR T-cells and anti-PD-1 therapy may lead to meaningful anti-tumor activity,” Amado said.
NY-ESO-1 is a cancer antigen, or molecule that can trigger an immune response against cancer. Researchers have found high levels of its expression in multiple myelomas that carry a bleak prognosis.
Adaptimune engineers patients’ T-cells to express a T-cell receptor that has a high affinity for — or desire to bond with — specific cancer proteins. The company calls the T-cell platform it developed SPEAR, for specific peptide enhanced affinity receptor.
It tested NYO-ESO spear in a previous Phase 1/2 single-arm clinical trial (NCT01352286) of 25 high-risk or relapsed myeloma patients with few remaining treatment options and low life expectancy. The treatment led to a complete response — or the disappearance of all signs of the cancer — in 70 percent of the patients within three months. Patients had high-dose chemotherapy and a stem cell transplant before receiving the modified T-cells.
The new open-label, randomized, pilot trial will evaluate the safety and effectiveness of NY-ESO SPEAR T-cells and Keytruda in 20 relapsed or refractory multiple myeloma patients. The 20 must express the NY-ESO-1 or LAGE-1a proteins, or both. They must also express cell-surface proteins known as HLA-A*02 that are involved in immune system regulation.
The trial participants will be randomized to receive either NY-ESO-1 alone or in a combination with Keytruda. The main objective of the study will be to determine which regimen works better.
Researchers will also be looking at the two regimens’ anti-tumor activity and how long the modified T-cells stay in the body.