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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04596033
• Other study ID #: GEN-011-101
• Status: Terminated
• Phase: Phase 1
• Start date: November 11, 2020
• Est. completion date: June 27, 2022

Study information

• Verified date: July 2022
• Source: Genocea Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: June 27, 2022
• Est. primary completion date: June 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anal Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Squamous Cell
• Cutaneous Squamous Cell Carcinoma
• Lung Neoplasms
• Melanoma
• Merkel Cell Carcinoma
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma

Intervention

Biological:
• GEN-011
Personalized neoantigen adoptive cell therapy (ACT)

Drug:
• IL-2
Cytokine
• Fludarabine
Lymphodepletion drug
• Cyclophosphamide
Lymphodepletion drug

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genocea Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immune cell phenotyping	Classification of peripheral immune cells via flow cytometry	2 years after first GEN-011 infusion
Other	Epitope Spread	Tumor mutations will be identified by gene sequencing at multiple timepoints, and comparing the differences in mutations over time	4 weeks after first GEN-011 infusion
Other	Tumor infiltrating immune cell	Quantitation and phenotyping of immune cells in proximity to tumor cells using immunohistochemistry	2 years after first GEN-011 infusion
Primary	Incidence of Treatment-Emergent Adverse Events	Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	2 years after first GEN-011 infusion
Secondary	T cell responses to GEN-011	Antigen-specific immunogenicity assays	2 years after first GEN-011 infusion
Secondary	Duration of response	Measured by RECIST	2 years after first GEN-011 infusion
Secondary	Progression-free survival	Length of time without disease progression	2 years after first GEN-011 infusion
Secondary	Overall survival	Length of time patient remains alive	From first GEN-011 infusion through study completion, at least 2 years