MelanomaPhase 1NCT04596033
TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy
A Phase 1 study testing GEN-011, IL-2 and Fludarabine in people with Melanoma and Non-small Cell Lung Cancer, run by Genocea Biosciences, Inc. at 8 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- GEN-011, IL-2 and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 8 sitesUnited States
- Study dates
- 11 Nov 2020to 27 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago Medical Center
Chicago, Illinois, 60637
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
MD Anderson Cancer Center
Houston, Texas, 77030
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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
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.
Read the 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.
- Conditions
- Melanoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma, Renal Cell Carcinoma, Small-cell Lung Cancer
- Being tested
- GEN-011, IL-2, Fludarabine, Cyclophosphamide
- Keywords
- Personalized, Immunotherapy, Solid Tumor, Personal, Cell Therapy, Carcinoma, Melanoma, Lung, Bladder, Cancer, Kidney, Anal, Squamous, TiTAN, ATLAS, PLANET, TiTAN-1, Autologous, Neoantigen
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Transitional Cell, Carcinoma, Renal Cell, Small Cell Lung Carcinoma, Anus Neoplasms, Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN-011Biological
Personalized neoantigen adoptive cell therapy (ACT)
IL-2Drug
Also called Interleukin-2
Cytokine
FludarabineDrug
Lymphodepletion drug
CyclophosphamideDrug
Lymphodepletion drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: GEN-011; Drug: IL-2 |
| 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. Receives: Biological: GEN-011; Drug: IL-2; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years after first GEN-011 infusion
Secondary outcomes (4)
T cell responses to GEN-011
Antigen-specific immunogenicity assays
Measured: 2 years after first GEN-011 infusion
Duration of response
Measured by RECIST
Measured: 2 years after first GEN-011 infusion
Progression-free survival
Length of time without disease progression
Measured: 2 years after first GEN-011 infusion
Overall survival
Length of time patient remains alive
Measured: From first GEN-011 infusion through study completion, at least 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start11 Nov 2020
- Primary completion27 Jun 2022
- Study completion27 Jun 2022
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genocea Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Davis, MD, Study director, Genocea Biosciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04596033
- Sponsor's protocol ID
- GEN-011-101
- Status last verified
- Jul 2022
- First submitted
- 30 Sep 2020
- Last updated
- 15 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04596033
- Acronym / sponsor ID
- GEN-011-101
- Conditions
- Melanoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Urothelial Carcinoma, Renal Cell Carcinoma, Small-cell Lung Cancer
- Keywords
- Personalized, Immunotherapy, Solid Tumor, Personal, Cell Therapy, Carcinoma, Melanoma, Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Genocea Biosciences, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Nov 2020 (actual)
- Primary completion
- 27 Jun 2022 (actual)
- Study completion
- 27 Jun 2022 (actual)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Multiple Low Dose (MLD) | Experimental | Biological: GEN-011, Drug: IL-2GEN-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 | Biological: GEN-011, Drug: IL-2, Drug: Fludarabine, Drug: CyclophosphamideGEN-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GEN-011Personalized neoantigen adoptive cell therapy (ACT) | Biological | Multiple Low Dose (MLD), Single High Dose (SHD) |
| IL-2Also: Interleukin-2Cytokine | Drug | Multiple Low Dose (MLD), Single High Dose (SHD) |
| FludarabineLymphodepletion drug | Drug | Single High Dose (SHD) |
| CyclophosphamideLymphodepletion drug | Drug | Single High Dose (SHD) |
Primary outcome
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
4 secondary outcomes
T cell responses to GEN-011
Time frame: 2 years after first GEN-011 infusion
Duration of response
Time frame: 2 years after first GEN-011 infusion
Progression-free survival
Time frame: 2 years after first GEN-011 infusion
Overall survival
Time frame: From first GEN-011 infusion through study completion, at least 2 years
Results and safety
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Davis, MD study director
Genocea Biosciences, Inc.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GEN-011, IL-2 and Fludarabine in people with Melanoma and Non-small Cell Lung Cancer, run by Genocea Biosciences, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 2 years after first GEN-011 infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2022.