*3.1.3 Published results*

*Advances in Precision Medicine Oncology*

**3.1 Immune Design: A Randomized, Open-Label, Phase II Trial of CMB305 (Sequentially Administered LV305 [lentiviral vector expressing NYESO-1 gene] and G305[NY-ESO-1 recombinant protein plus GLA-SE]) and Atezolizumab in Patients with Locally Advanced, Relapsed, or Metastatic Sarcoma Expressing NY-ESO-1 (NCT02609984) Sant P. Chawla, Principal** 

NY-ESO-1 is a protein that is normally expressed in fetal and testicular tissues, although some solid malignancies have been known to express an abnormal NY-ESO-1 protein that has become a target for emerging antigen-directed cancer therapies [43, 44]. Previous studies looking at NY-ESO-1 expression in cancer cells have reported its presence in the majority of synovial sarcomas tested, as well as sporadic expression in a number of other sarcoma subsets [45]. The immunogenicity of NY-ESO-1 has been demonstrated by the discovery of receptors against

Institute was the first to report promising anticancer effects of NY-ESO-1-targeted immunotherapy in patients with metastatic synovial sarcoma using adoptively transferred autologous T-cells containing a T-cell receptor against NY-ESO-1 [46], suggesting its potential to be effective in other sarcomas as well. Since then, numerous trials targeting NY-ESO-1 in various cancer types using both adoptive T-cell therapy and vaccination approaches have concluded that there is a clear clinical

The drug being studied is CMB305, a prime-boost immunotherapeutic vaccine regimen developed to prime the immune system and enhance its subsequent response to immunotherapeutic agents. The priming component of CMB305 is an integration-deficient, replication-incompetent lentiviral vector containing RNA coding for NY-ESO-1. The boost component contains a recombinant E. coli-produced NY-ESO-1 protein that, as a single agent, can initiate anti-NY-ESO-1-specific

T-cell and antibody responses. The combination of the primer and the booster

T-cells to synergisti-

The goal of this study was to investigate the ability of a prime-boost immuno-

cally enhance the efficacy of PD-L1 checkpoint inhibition therapy in advanced or metastatic sarcoma patients whose tumors are positive for NY-ESO-1 expression.

The primary objective of this study was to compare the progression-free survival in locally advanced or metastatic sarcoma patients whose tumors expressed NY-ESO-1 when treated with CMB305 in combination with atezolizumab versus patients treated with atezolizumab alone. The secondary objectives of this study were to evaluate the safety of this combination treatment, as well as to evaluate the best overall response rate using RECIST v1.1 modified to use immune-related response criteria. The overall survival of the two groups will be evaluated. Twelve patients were randomized 1:1 in a safety run-in evaluation. Next, 80 patients were randomized and stratified by disease. Tumor samples from all patients were tested for levels of PD-L1 and NY-ESO-1 expression prior to treatment, and again on Day 42 in order to assess the extent of successful immune cell invasion in the tumor. Re-staging imaging studies were performed every six

benefit in pursuing NY-ESO-1 as an immunotherapeutic target [47].

was designed with the intention of eliciting an enhanced T-cell response.

therapy regimen that is able to elicit NY-ESO-1-specific CD8+

T-cells. A 2011 clinical trial conducted by the National Cancer

**3. Past clinical research**

**Investigator**

NY-ESO-1 on CD8+

*3.1.1 Background & rationale*

**14**

CD4+

*3.1.2 Methods*

Not Available.

#### *3.1.4 Conclusions/future directions*

Phase I of this trial was the first of its kind to test a prime-boost vaccination regimen to treat patients with advanced cancer. In 2018, Immune Design released information stating that an early analysis of the Phase II clinical trial results showed the combination treatment of atezolizumab with CMB305 suggested that it is unlikely this regimen will show enhanced survival time of patients with recurrent synovial sarcoma [48]. A Phase III trial has not yet been pursued.
