Clinical trial NCT04596033: TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy
Official title: A Phase 1 Study to Evaluate the Safety, Proliferation and Persistence of GEN-011, an Autologous Adoptive Cell Therapy Targeting Neoantigens in Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Melanoma
Non-small Cell Lung Cancer
Squamous Cell Carcinoma of Head and Neck
Urothelial Carcinoma
Renal Cell Carcinoma
Small-cell Lung Cancer
Cutaneous Squamous Cell Carcinoma
Anal Squamous Cell Carcinoma
Merkel Cell Carcinoma
Keywords: Personalized
Immunotherapy
Solid Tumor
Personal
Cell Therapy
Carcinoma
Melanoma
Lung
Bladder
Cancer
Kidney
Anal
Squamous
TiTAN
ATLAS
PLANET
TiTAN-1
Autologous
Neoantigen
Lead sponsor: Genocea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 2 years after first GEN-011 infusion
Secondary outcomes:
measure: T cell responses to GEN-011
timeFrame: 2 years after first GEN-011 infusion
measure: Duration of response
timeFrame: 2 years after first GEN-011 infusion
measure: Progression-free survival
timeFrame: 2 years after first GEN-011 infusion
measure: Overall survival
timeFrame: From first GEN-011 infusion through study completion, at least 2 years
Other outcomes:
measure: Immune cell phenotyping
timeFrame: 2 years after first GEN-011 infusion
measure: Epitope Spread
timeFrame: 4 weeks after first GEN-011 infusion
measure: Tumor infiltrating immune cell
timeFrame: 2 years after first GEN-011 infusion
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Genocea Biosciences, Inc.
name: Thomas Davis, MD
role: STUDY_DIRECTOR
References: