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

Primary Purpose

Melanoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GEN-011
IL-2
Fludarabine
Cyclophosphamide
Sponsored by
Genocea Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Personalized, Immunotherapy, Solid Tumor, Personal, Cell Therapy, Carcinoma, Melanoma, Lung, Bladder, Cancer, Kidney, Anal, Squamous, TiTAN, ATLAS, PLANET, TiTAN-1, Autologous, Neoantigen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Banner MD Anderson Cancer Center
  • Moffitt Cancer Center
  • University of Chicago Medical Center
  • Dana Farber Cancer Institute
  • Columbia University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Sarah Cannon Research Institute
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Multiple Low Dose (MLD)

Single High Dose (SHD)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

T cell responses to GEN-011
Antigen-specific immunogenicity assays
Duration of response
Measured by RECIST
Progression-free survival
Length of time without disease progression
Overall survival
Length of time patient remains alive

Full Information

First Posted
September 30, 2020
Last Updated
July 13, 2022
Sponsor
Genocea Biosciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04596033
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Business reasons
Study Start Date
November 11, 2020 (Actual)
Primary Completion Date
June 27, 2022 (Actual)
Study Completion Date
June 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genocea Biosciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Multiple Low Dose (MLD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Single High Dose (SHD)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
GEN-011
Intervention Description
Personalized neoantigen adoptive cell therapy (ACT)
Intervention Type
Drug
Intervention Name(s)
IL-2
Other Intervention Name(s)
Interleukin-2
Intervention Description
Cytokine
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Lymphodepletion drug
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Lymphodepletion drug
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time Frame
2 years after first GEN-011 infusion
Secondary Outcome Measure Information:
Title
T cell responses to GEN-011
Description
Antigen-specific immunogenicity assays
Time Frame
2 years after first GEN-011 infusion
Title
Duration of response
Description
Measured by RECIST
Time Frame
2 years after first GEN-011 infusion
Title
Progression-free survival
Description
Length of time without disease progression
Time Frame
2 years after first GEN-011 infusion
Title
Overall survival
Description
Length of time patient remains alive
Time Frame
From first GEN-011 infusion through study completion, at least 2 years
Other Pre-specified Outcome Measures:
Title
Immune cell phenotyping
Description
Classification of peripheral immune cells via flow cytometry
Time Frame
2 years after first GEN-011 infusion
Title
Epitope Spread
Description
Tumor mutations will be identified by gene sequencing at multiple timepoints, and comparing the differences in mutations over time
Time Frame
4 weeks after first GEN-011 infusion
Title
Tumor infiltrating immune cell
Description
Quantitation and phenotyping of immune cells in proximity to tumor cells using immunohistochemistry
Time Frame
2 years after first GEN-011 infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Davis, MD
Organizational Affiliation
Genocea Biosciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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