William D. Tap, MD
Investigators are hopeful that CMB305, a vaccine that boosts the immune response to tumor cells expressing the antigen NY-ESO-1, can improve survival outcomes for patients with synovial sarcoma, a rare subtype of soft tissue sarcoma that primarily develops in the arms and legs and affects about 800 individuals in the United States each year. Patients with advanced disease have poor odds for survival, and even good responses to standard chemotherapy can often last just a few months.
“We know [that] patients with synovial sarcoma, especially when they present with locally advanced or metastatic disease, are often not curable,” said William D. Tap, MD, chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York, New York. He said that after patients stop chemotherapy treatment, their disease often progresses. Clinicians can often re-treat with chemotherapy, but due to the toxicities, this is not always an option, and there are limited agents available for subsequent lines of therapy.
In the phase III Synovate Study, CMB305 will be tested as maintenance monotherapy in patients with locally advanced, unresectable, or metastatic synovial sarcoma after initial treatment with chemotherapy (NCT03520959). Investigators seek to enroll approximately 248 patients who have achieved at least stable disease (Figure
Eligible participants must have expression of the NY-ESO-1 surface protein, which is commonly found in synovial sarcoma tumors and is shown by immunohistochemical testing. CMB305 combines 2 mechanisms of action in 1 vaccine targeting the antigen NY-ESO-1. The prime component is an engineered lentiviral vector that binds to dendritic cells (DCs), causing them to express NY-ESO-1, thereby boosting the immune response against NY-ESO-1–expressing tumor cells.2
Figure. CMB305 in Synovial Sarcoma
The second component of the vaccine, G305, is a toll-like receptor (TLR)–4 agonist, which also boosts the immune system. G305 binds to TLR-4 on immune cells, including DCs, and induces an NY-ESO-1-specific antibody response,2
impeding tumor cell proliferation and survival.
“It’s the combination of these 2 components [that] can make [CMB305] very potent, [prompting] the immune system to recognize and want to go after cells that express NY-ESO-1 protein,” said Tap, who is one of the lead international coordinating investigators and chair of the international steering committee for the phase III trial.