The purpose of this study is to evaluate the dose, safety, immunogenicity and early clinical activity of GRT-C903 and GRT-R904, a neoantigen-based therapeutic cancer vaccine, in combination with immune checkpoint blockade, in patients with advanced or metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, pancreatic cancer, and shared neoantigen-positive tumors. Based on the Phase 1 data, an updated vaccine candidate (SLATE-KRAS or version 2) was developed that removed 16 of the 20 mutations included in the original vaccine (version 1) and solely targets KRAS mutations.
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. Some of these tumor-specific neoantigens are known or expected to be common across a subset of patients and are called shared neoantigens. This study aims to target shared neoantigens using a heterologous prime/boost therapeutic vaccine approach (GRT-C903 first followed by GRT-R904) in combination with checkpoint blockade to stimulate an immune response. This study will explore the safety and early clinical activity of this neoantigen-based immunotherapy intended to induce T-cell responses specific for the shared neoantigens contained within the therapeutic vaccine. Phase 1 will test multiple doses and combinations with checkpoint blockade and Phase 2 will test for early signs of clinical activity using a vaccine regimen based on Phase 1 data.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
a shared neoantigen cancer vaccine prime
a shared neoantigen cancer vaccine boost
anti-PD-1 monoclonal antibody
anti-CTLA-4 monoclonal antibody
Mayo Clinic Arizona
Phoenix, Arizona, United States
UCLA Medical Center
Santa Monica, California, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
University of Chicago Medicine, Comprehensive Cancer Center
Chicago, Illinois, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Tennessee Oncology
Nashville, Tennessee, United States
...and 2 more locations
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-C903 and GRT-R904
Time frame: Up to approximately 6 months
Measure the immune response to the neoantigens encoded by GRT-C903 and GRT-R904
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 27 months)
Duration of response (DOR) using RECIST v1.1
Time frame: Initiation of study treatment until disease progression (up to approximately 27 months)
Clinical benefit rate (CBR) using RECIST v1.1
Time frame: Initiation of study treatment until disease progression (up to approximately 27 months)
Progression-free survival (PFS)
Time frame: Up to approximately 4 years
Overall survival (OS)
Time frame: Up to approximately 4 years
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