Immune Design, a clinical-stage immunotherapy company, has entered into a clinical trial collaboration with Genentech, a member of the Roche Group, to evaluate the safety and efficacy of Immune Design's CMB305 cancer immunotherapy product candidate combined with the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) in a randomized phase 2 trial in patients with soft tissue sarcoma.
CMB305 is a 'prime-boost' cancer immunotherapy product designed to synergistically induce anti-tumour cytotoxic T lymphocytes (CTLs) to target NY-ESO-1, a tumour antigen found in a broad set of tumours. Atezolizumab is a PD-L1 antagonist and is designed to block inhibitory T-cell checkpoints and allow cytotoxic T cells to reach the tumour. The randomized, open label phase 2 trial will evaluate CMB305 and atezolizumab in patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid/round-cell liposarcoma, two types of sarcoma that tend to express NY-ESO-1 broadly.
"The combination of CMB305, which is designed to generate and expand tumour-specific CD8 T cells, with atezolizumab, which is designed to remove the tumour-induced blockade, makes profound sense from a mechanistic perspective," said Carlos Paya, M.D., Ph.D., president and chief executive officer of Immune Design.
"We are pleased to begin this collaboration with Genentech and explore the potential synergy of these product candidates, which will hopefully bring significant benefit to patients."
CMB305 is a cancer immunotherapy product candidate combining two potentially synergistic agents, LV305 and G305. LV305 is a hybrid vector from the ZVex discovery platform that specifically targets dendritic cells (DCs) in vivo and delivers the RNA for NY-ESO-1, enabling the DCs to express the entire tumour antigen and potentially induce a diverse set of CTLs targeting NY-ESO-1. G305, in contrast, is designed to boost the CTL response via the induction of antigen-specific CD4 "helper" T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of the GLAAS platform. CMB305 is intended to be an "off-the shelf" therapy that does not require patient-specific manufacturing or ex vivo manipulation of patient samples. Having established the safety and individual immunologic activity of LV305 and G305 in prior studies, Immune Design initiated a new phase 1B study of the product candidate CMB305 earlier this year.
Soft Tissue Sarcomas (STS) are malignancies that arise from the soft tissues of the body, such as tissues that connect, support and surround other body structures including muscle, fat, blood vessels, nerves, tendons and the lining of joints. In the United States, nearly 12,000 people will be diagnosed and approximately 4,870 are expected to die of STS in 2015. There are approximately 50 different types of STS including liposarcomas and synovial sarcomas, which are subtypes effecting fat tissue and tissue around the joints, respectively. Myxoid/round cell is a type of liposarcoma that accounts for approximately 30 per cent of all liposarcoma cases. Myxoid and round cell liposarcoma and synovial sarcomas have been shown to have high expression of NY-ESO-1, approximately 90 per cent and approximately 50 per cent, respectively.