Clinical Trials /

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

NCT04596033

Description:

GEN-011 is 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 finds which cancer proteins are recognized already by the patient's T cells using ATLAS™. Then, immune cells that recognize these cancer proteins are multiplied many times to create the GEN-011 cell therapy. The personalized GEN-011 is then given back to the patient in one or more intravenous (IV) infusions.

Related Conditions:
  • Anal Squamous Cell Carcinoma
  • Cutaneous Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GEN-011-101
  • NCT ID: NCT04596033

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

Interventions

DrugSynonymsArms
GEN-011Multiple Low Dose (MLD)
IL-2Interleukin-2Multiple Low Dose (MLD)
FludarabineSingle High Dose (SHD)
CyclophosphamideSingle High Dose (SHD)

Purpose

GEN-011 is 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 finds which cancer proteins are recognized already by the patient's T cells using ATLAS™. Then, immune cells that recognize these cancer proteins are multiplied many times to create the GEN-011 cell therapy. The personalized GEN-011 is then given back to the patient in one or more intravenous (IV) infusions.

Detailed Description

      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.

      This 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.
    

Trial Arms

NameTypeDescriptionInterventions
Multiple Low Dose (MLD)ExperimentalGEN-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
  • IL-2
Single High Dose (SHD)ExperimentalGEN-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.
  • GEN-011
  • IL-2
  • Fludarabine
  • Cyclophosphamide

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)

          -  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 arrythmias 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:2 years after first GEN-011 infusion
Safety Issue:
Description:Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genocea Biosciences, Inc.

Trial Keywords

  • Personalized
  • Immunotherapy
  • Solid Tumor
  • Personal
  • Cell Therapy
  • Carcinoma
  • Melanoma
  • Lung
  • Bladder
  • Cancer
  • Kidney
  • Anal
  • Squamous

Last Updated

October 15, 2020