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

July 13, 2022 updated by: Genocea Biosciences, Inc.

A Phase 1 Study to Evaluate the Safety, Proliferation and Persistence of GEN-011, an Autologous Adoptive Cell Therapy Targeting Neoantigens in Solid Tumors

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Multiple Low Dose (MLD)
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.
Biological: GEN-011
Personalized neoantigen adoptive cell therapy (ACT)
Drug: IL-2
Cytokine
Other Names:
  • Interleukin-2
EXPERIMENTAL: Single High Dose (SHD)
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.
Biological: GEN-011
Personalized neoantigen adoptive cell therapy (ACT)
Drug: IL-2
Cytokine
Other Names:
  • Interleukin-2
Drug: Fludarabine
Lymphodepletion drug
Drug: Cyclophosphamide
Lymphodepletion drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events
Time Frame: 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
2 years after first GEN-011 infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T cell responses to GEN-011
Time Frame: 2 years after first GEN-011 infusion
Antigen-specific immunogenicity assays
2 years after first GEN-011 infusion
Duration of response
Time Frame: 2 years after first GEN-011 infusion
Measured by RECIST
2 years after first GEN-011 infusion
Progression-free survival
Time Frame: 2 years after first GEN-011 infusion
Length of time without disease progression
2 years after first GEN-011 infusion
Overall survival
Time Frame: From first GEN-011 infusion through study completion, at least 2 years
Length of time patient remains alive
From first GEN-011 infusion through study completion, at least 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune cell phenotyping
Time Frame: 2 years after first GEN-011 infusion
Classification of peripheral immune cells via flow cytometry
2 years after first GEN-011 infusion
Epitope Spread
Time Frame: 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
4 weeks after first GEN-011 infusion
Tumor infiltrating immune cell
Time Frame: 2 years after first GEN-011 infusion
Quantitation and phenotyping of immune cells in proximity to tumor cells using immunohistochemistry
2 years after first GEN-011 infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genocea Biosciences, Inc.

Investigators

  • Study Director: Thomas Davis, MD, Genocea Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 11, 2020

Primary Completion (ACTUAL)

June 27, 2022

Study Completion (ACTUAL)

June 27, 2022

Study Registration Dates

First Submitted

September 30, 2020

First Submitted That Met QC Criteria

October 15, 2020

First Posted (ACTUAL)

October 22, 2020

Study Record Updates

Last Update Posted (ACTUAL)

July 15, 2022

Last Update Submitted That Met QC Criteria

July 13, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEN-011-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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