Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered LV305 \[a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene\] and G305 \[NY-ESO-1 recombinant protein plus GLA-SE\]) in patients with melanoma, sarcoma, ovarian cancer, or non-small cell lung cancer that express NY-ESO-1.

This study is designed to investigate and examine the safety and immunogenicity of the combinatorial regimen called CMB305, where intradermal LV305 is administered sequentially with intramuscular G305 over three months. During Part 1, a dose escalation design will be utilized in patients with melanoma, NSCLC, ovarian cancer, or sarcoma. After completion of Part 1, the study will be expanded in Part 2 and will enroll patients with NSCLC, ovarian cancer, synovial sarcoma or myxoid/round cell liposarcoma. While this is an exploratory study to evaluate the safety, tolerability and immunogenicity of the CMB305 regimen, the study will also evaluate the safety and response to with oral metronomic CPA or intratumoral G100 in the context of CMB305. CMB305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors, designed to generate an integrated, anti-NY-ESO-1 immune response in vivo via a targeted, specific interaction with dendritic cells. G100 contains a potent synthetic small molecule toll-like receptor-4 (TLR-4) agonist, Glucopyranosyl Lipid A (GLA) that leverages the activation of both innate and adaptive immunity, including dendritic cells, in the tumor microenvironment to create an immune response against the tumor's preexisting diverse set of antigens.