TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy

A Phase 1 Study to Evaluate the Safety, Proliferation and Persistence of GEN-011, an Autologous Adoptive Cell Therapy Targeting Neoantigens in Solid Tumors

TiTAN-1 is a first-in-human study of GEN-011, an experimental treatment being evaluated in adult patients with advanced cancer. GEN-011 is a T cell therapy made specific to each patient, using the patient's own circulating immune cells. First, Genocea confirms which cancer proteins are recognized already by each patient's T cells using ATLAS™. Then, immune cells that recognize these cancer proteins are multiplied many times (a process called PLANET™) to create a personalized GEN-011 cell therapy, which is given back to the patient in one or more intravenous (IV) infusions.

TiTAN-1 is an open-label, multicenter, first-in-human Phase 1 study of GEN-011 in patients with melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC, bladder, ureter, urethra, or renal pelvis), renal cell carcinoma (RCC), small cell lung cancer (SCLC), cutaneous squamous cell carcinoma (CSCC), or anal squamous cell carcinoma (ASCC). Patients will be enrolled into one of 2 cohorts. One cohort will receive a multiple low dose (MLD) regimen of GEN-011 to be given without lymphodepletion, and a second cohort will receive a single high dose (SHD) regimen of GEN-011 after lymphodepletion. Regardless of cohort, each dose of GEN-011 will be followed by a course of interleukin-2 (IL-2) as costimulatory therapy.

GEN-011 is an investigational, personalized neoantigen adoptive cell therapy (ACT) that is being developed by Genocea for the treatment of adult patients with advanced solid tumors. A proprietary tool developed by Genocea called ATLAS™ (Antigen Lead Acquisition System) will be used to identify true immunogenic neoantigens from each patient's tumor that are recognized by their own CD4 and/or CD8 T cells. ATLAS-identified neoantigens will be used to stimulate and select autologous T cells collected by apheresis to generate an adoptive cell product ex vivo.

Inclusion Criteria:

• Consents to study procedures
• Diagnosis of one of the following solid tumors: cutaneous melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), renal cell carcinoma (RCC), small cell lung cancer (SCLC), cutaneous squamous cell carcinoma (CSCC), anal squamous cell carcinoma (ASCC), merkel cell carcinoma (MCC).
• Received, been intolerant of, or been ineligible to receive standard of care treatment regimen.
• Measurable disease per RECIST criteria
• Life expectancy > 6 months and ECOG status 0 or 1
• Capacity to tolerate lymphodepletion (SHD group only) and IL-2 therapy
• Tumor tissue available
• Willing to use contraceptives for 90 days after receiving GEN-011, and not currently pregnant.
• Adequate blood, liver, kidney, and lung function
• Sufficient stimulatory neoantigens identified in ATLAS

Exclusion Criteria:

• Receiving immunosuppressive medications
• Serious ongoing viral, bacterial, or fungal infection
• History of cardiac arrhythmias or significant heart block
• History of leptomeningeal carcinomatosis
• Active autoimmune disease
• Portal vein thrombosis
• Malignant disease other than those treated in this study
• Receiving other investigational anti-cancer therapy
• Prior stem cell or solid organ transplant
• Primary immune deficiency disease
• Significant ongoing toxicities from prior therapies
• A history of allergic reaction to sulfur derivatives