LV305 is a novel therapy being developed by Immune Design to stimulate the patients’ own immune system against specific cancer cells that have high levels of a protein called NY-ESO-1. Normally found in the testes, NY-ESO-1 levels are increased in certain cancers, such as melanoma, sarcoma, ovarian cancer, and small cell lung cancer (SCLC).

LV305 is an engineered harmless virus that targets a type of immune cells called dendritic cells (DCs). The virus contains genetic material that encodes for the cancer-testis antigen NY-ESO-1.

LV305 is also one of the components of another treatment called CMB305. This treatment consists of sequentially administrated LV305 and G305, another cancer vaccine.

How LV305 works

LV305 is administered into the skin, where it binds to dendritic cells via a receptor called the DC-SIGN receptor. The virus is then taken up by the dendritic cells, enabling the production of NY-ESO-1 protein. The NY-ESO-1 production stimulates dendritic cell maturation and activates the immune system to send cytotoxic (or cell-killing) T- cells to destroy the NY-ESO-1-positive cancer cells.

LV305 in clinical trials

LV305 is currently being evaluated in Phase 1 and 2 clinical trials in cancer patients whose NY-ESO-1-positive, solid tumor has spread to different parts of the body and whose disease has returned. The vaccine is either being used as a single agent or in combination with other cancer drugs.

An open-label, multicenter Phase 1 study (NCT02122861) is evaluating the safety and immunogenicity (ability to trigger an immune response) of LV305 in patients with locally advanced, returning, or metastatic cancer that express NY-ESO-1, including melanoma, sarcoma, ovarian cancer, and SCLC.

The trial is assessing the effect of LV305 together with Keytruda (pembrolizumab) — an anti-PD-1 therapy that boosts the immune response against cancer cells — in patients with melanoma who have inadequately responded to Keytruda alone. The primary purpose is to determine the dose of LV305 that can be given safely to patients.

The treatment is injected into the skin every three weeks for four doses. The study has two parts. In part 1, which is the dose escalation part, three sequentially enrolled groups of patients are treated at one of four dose levels of LV305 using a standard escalation design. This is followed by a part 2 expansion, where an additional 27 patients are enrolled.

Results so far have shown that the first patient treated with LV305, a young woman with metastatic and recurrent synovial sarcoma, developed a robust NY-ESO-1-specific T-cell response after three injections of LV305. Subsequently, she experienced more than 85 percent disease regression, which has been going on for more than 2.5 years after the therapy, without any adverse events. This result suggests that LV305 is safe and has the potential to induce a significant immune response in a patient with advanced-stage cancer.

LV305 is also being studied as a component of CMB305 in an open-label, multicenter Phase 1 study (NCT02387125) that aims to evaluate the safety and immunogenicity of CMB305 in patients with advanced cancer expressing NY-ESO-1.

Positive data were reported from this study at the American Society of Clinical Oncology’s (ASCO) 2017 Annual Meeting. CMB305 was well tolerated, and generated a strong anti-NY-ESO-1 immune response in more than 50 percent of the patients, with significant tumor growth arrest. The overall survival rate was 83 percent and 76 percent at 12 and 18 months, respectively. While both LV305 and CMB305 induced the immune system, CMB305 resulted in a stronger and broader integrated immune response.

Another ongoing, fully enrolled, open-label, randomized Phase 2 study (NCT02609984) is evaluating the safety and efficacy of CMB305 in combination with Tecentriq (atezolizumab), or Tecentriq alone, in 88 patients with advanced sarcoma (synovial sarcoma or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein. Tecentriq is an immune checkpoint inhibitor.

An interim analysis of this trial showed that the patients receiving the combination of CMB305 and Tecentriq experienced greater clinical benefit, more robust immune response, and improved overall survival than those receiving Tecentriq alone. The combination was observed to be well tolerated by participants.


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