Anal Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Melanoma, Merkel Cell Carcinoma, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Small-cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma
Conditions
Keywords
Personalized, Immunotherapy, Solid Tumor, Personal, Cell Therapy, Carcinoma, Melanoma, Lung, Bladder, Cancer, Kidney, Anal, Squamous, TiTAN, ATLAS, PLANET, TiTAN-1, Autologous, Neoantigen
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALGEN-011
Personalized neoantigen adoptive cell therapy (ACT)
DRUGIL-2
Cytokine
DRUGFludarabine
Lymphodepletion drug
DRUGCyclophosphamide
Lymphodepletion drug
Sponsors
Genocea Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 2 years after first GEN-011 infusion | Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | 2 years after first GEN-011 infusion | Measured by RECIST |
| T cell responses to GEN-011 | 2 years after first GEN-011 infusion | Antigen-specific immunogenicity assays |
| Progression-free survival | 2 years after first GEN-011 infusion | Length of time without disease progression |
| Overall survival | From first GEN-011 infusion through study completion, at least 2 years | Length of time patient remains alive |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor infiltrating immune cell | 2 years after first GEN-011 infusion | Quantitation and phenotyping of immune cells in proximity to tumor cells using immunohistochemistry |
| Epitope Spread | 4 weeks after first GEN-011 infusion | Tumor mutations will be identified by gene sequencing at multiple timepoints, and comparing the differences in mutations over time |
| Immune cell phenotyping | 2 years after first GEN-011 infusion | Classification of peripheral immune cells via flow cytometry |
Countries
United States
Outcome results
None listed