Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Sarcoma

Neoplastic Processes

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Patients with melanoma, NSCLC, ovarian cancer, or sarcoma will be enrolled. Patients will receive CMB305, a sequential regimen of LV305 and G305. Two cohorts are planned based on LV305 dose.

Arm A will enroll up to 9 patients each with NSCLC or ovarian cancer, or up to 18 patients with the sarcoma subtypes, synovial sarcoma or MRCL. Arm B will enroll up to 9 additional patients with selected sarcoma subtypes to explore subcutaneous (SC) dosing of LV305 and G305 on the same schedule. Arm C will enroll up to 9 patients with synovial sarcoma or MRCL for treatment with CMB305 and with oral metronomic CPA. Arm D will enroll up to 9 patients with synovial sarcoma or MRCL at selected sites for treatment with CMB305 and IT G100. Arm E will enroll up to 6 patients with soft tissue sarcoma any subtype for treatment with a higher dose of CMB305 than previous arms.

CMB305

G100

Metronomic CPA

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.

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

A Phase 1b Study Evaluating the Safety, Tolerability and Immunogenicity of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

To evaluate the safety and tolerability of CMB305 (sequential administered doses of LV305 and G305) alone or in combination with oral metronomic CPA or G100 in subjects with locally advanced, relapsed, or metastatic cancer expressing NY ESO 1

To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity

Overall survival (OS), time to progression (TTP), and progression-free survival (PFS) and descriptive tumor responses. Evaluation of response will be by RECIST (v1.1) modified to use irRC measurement criteria and by changes in markers of tumor burden

To evaluate the cellular and humoral immunogenicity of CMB305 alone or in combination with mCPA or G100 in patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1	NCT02387125	Sarcoma Melanoma Non-small Cell ... Ovarian Cancer	CMB305 G100 Metronomic CPA	18 Years - 80 Years	Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1	NCT02387125	Sarcoma Melanoma Non-small Cell ... Ovarian Cancer	CMB305 G100 Metronomic CPA	18 Years - 80 Years	Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

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