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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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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

Intervention / Treatment
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* Biological: GEN-011
* Drug: IL-2
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiple Low Dose (MLD)<br>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<br>* Personalized neoantigen adoptive cell therapy (ACT)<br>Drug: IL-2<br>* Cytokine<br>* Other names: Interleukin-2;|
| Experimental: Single High Dose (SHD)<br>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<br>* Personalized neoantigen adoptive cell therapy (ACT)<br>Drug: IL-2<br>* Cytokine<br>* Other names: Interleukin-2;Drug: Fludarabine<br>* Lymphodepletion drug<br>Drug: Cyclophosphamide<br>* Lymphodepletion drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 years after first GEN-011 infusion | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Personalized, Immunotherapy, Solid Tumor, Personal, Cell Therapy, Carcinoma, Melanoma, Lung, Bladder, Cancer, Kidney, Anal, Squamous, TiTAN, ATLAS, PLANET, TiTAN-1, Autologous, Neoantigen