TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy
- Conditions
- MelanomaNon-small Cell Lung CancerRenal Cell CarcinomaSmall-cell Lung CancerCutaneous Squamous Cell CarcinomaSquamous Cell Carcinoma of Head and NeckUrothelial CarcinomaAnal Squamous Cell CarcinomaMerkel Cell Carcinoma
- Interventions
- Registration Number
- NCT04596033
- Lead Sponsor
- Genocea Biosciences, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Single High Dose (SHD) IL-2 GEN-011 is administered as a single IV infusion at the maximum available cell yield, after the patient completes a fludarabine/cyclophosphamide lymphodepletion regimen. The single GEN-011 dose is followed by IL-2 administration. Multiple Low Dose (MLD) GEN-011 GEN-011 is administered by IV infusion at 4-week intervals, up to 5 doses maximum. Each dose is followed by IL-2 administration. MLD patients will not undergo lymphodepletion. Multiple Low Dose (MLD) IL-2 GEN-011 is administered by IV infusion at 4-week intervals, up to 5 doses maximum. Each dose is followed by IL-2 administration. MLD patients will not undergo lymphodepletion. Single High Dose (SHD) GEN-011 GEN-011 is administered as a single IV infusion at the maximum available cell yield, after the patient completes a fludarabine/cyclophosphamide lymphodepletion regimen. The single GEN-011 dose is followed by IL-2 administration. Single High Dose (SHD) Cyclophosphamide GEN-011 is administered as a single IV infusion at the maximum available cell yield, after the patient completes a fludarabine/cyclophosphamide lymphodepletion regimen. The single GEN-011 dose is followed by IL-2 administration. Single High Dose (SHD) Fludarabine GEN-011 is administered as a single IV infusion at the maximum available cell yield, after the patient completes a fludarabine/cyclophosphamide lymphodepletion regimen. The single GEN-011 dose is followed by IL-2 administration.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (8)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States