The purpose of this study is to evaluate the safety, dose, immunogenicity and early clinical activity of GRT-C901 and GRT-R902, a personalized neoantigen cancer vaccine, in combination with nivolumab and ipilimumab, in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer.
Tumors harboring non-synonymous deoxyribonucleic acid (DNA) mutations can present peptides containing these mutations as non-self antigens in the context of HLA on the tumor cell surface. A fraction of mutated peptides result in neoantigens capable of generating T-cell responses that exclusively target tumor cells. Sensitive detection of these mutations allows for the identification of neoantigens unique to each patient's tumor to be included in a personalized cancer vaccine that targets these neoantigens. This vaccine regimen uses two vaccine vectors as a heterologous prime/boost approach (GRT-C901 first followed by GRT-R902) to stimulate an immune response. This study will explore the safety and early clinical activity of this patient-specific immunotherapy intended to induce T-cell responses specific for neoantigens.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Mayo Clinic Arizona
Phoenix, Arizona, United States
Mayo Clinic
Jacksonville, Florida, United States
The University of Chicago
Chicago, Illinois, United States
Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Time frame: Initiation of study treatment through 100 days post-last dose (up to approximately 27 months)
Objective Response Rate (ORR) in Phase 2 using RECIST v1.1
Time frame: Initiation of study treatment until disease progression (up to approximately 27 months)
Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902
Time frame: Up to approximately 6 months
Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902
Time frame: Baseline to end of treatment (up to approximately 12 months)
Objective Response Rate (ORR) in Phase 1 using RECIST v1.1
Time frame: Initiation of study treatment until disease progression (up to approximately 4 years)
Duration of response (DOR) using RECIST v1.1
Time frame: Initiation of study treatment until disease progression (up to approximately 4 years)
Clinical benefit rate (using RECIST v1.1)
Time frame: Initiation of study treatment until disease progression (up to approximately 4 years)
Progression-free survival (PFS)
Time frame: Up to approximately 4 years
Overall survival (OS)
Time frame: Up to approximately 4 years
Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing
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anti-CTLA-4 monoclonal antibody
Mayo Clinic
Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Tennessee Oncology
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
...and 1 more locations
Time frame: Study enrollment to initiation of study treatment (up to approximately 6 months)