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.
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
| Drug | Synonyms | Arms |
|---|
| GEN-011 | | Multiple Low Dose (MLD) |
| IL-2 | Interleukin-2 | Multiple Low Dose (MLD) |
| Fludarabine | | Single High Dose (SHD) |
| Cyclophosphamide | | Single 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
| Name | Type | Description | Interventions |
|---|
| Multiple Low Dose (MLD) | Experimental | 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. | |
| Single High Dose (SHD) | Experimental | 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. | - 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
