Colorectal Cancer, Gastroesophageal Adenocarcinoma, Non Small Cell Lung Cancer, Urothelial Carcinoma
Conditions
Keywords
neoantigen cancer vaccine, personalized neoantigen cancer vaccine, GRT-C901, GRT-R902, immunotherapy, nivolumab, ipilimumab, PD-1, CTLA-4
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
Bristol-Myers Squibb
Gritstone bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide a signed and dated informed consent form prior to initiation of study-specific procedures. * Patients with the indicated advanced or metastatic solid tumor as follows: 1. NSCLC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy (note: patients who have received anti-PD-(L)1 monotherapy are eligible) 2. GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy 3. mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy 4. CRC-MSS who are receiving first line systemic therapy or who are planned for or have received no more than 1 cycle of second line systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan * 18 years of age or older * ECOG Performance Status 0 or 1 * Lesion amenable to biopsy * Measurable disease according to RECIST v1.1 * Have adequate organ function, as measured by laboratory values (criteria listed in protocol)
Exclusion criteria
* Tumors with genetic characteristics as follows: 1. For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK 2. For CRC and GEA, patients with known MSI-high disease based on institutional standard 3. For CRC, patients with a known BRAF V600E mutation or patients with peritoneal carcinomatosis and for GEA, patients with peritoneal carcinomatosis as their only evidence of disease * Patients with known central nervous system (CNS) metastases and/or carcinomatous meningitis * Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination or allergy or hypersensitivity to study drug components * Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws Complete inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) | 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 | 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 | Up to approximately 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Clinical benefit rate (using RECIST v1.1) | Initiation of study treatment until disease progression (up to approximately 4 years) |
| Progression-free survival (PFS) | Up to approximately 4 years |
| Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902 | Baseline to end of treatment (up to approximately 12 months) |
| Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing | Study enrollment to initiation of study treatment (up to approximately 6 months) |
| Overall survival (OS) | Up to approximately 4 years |
| Objective Response Rate (ORR) in Phase 1 using RECIST v1.1 | Initiation of study treatment until disease progression (up to approximately 4 years) |
| Duration of response (DOR) using RECIST v1.1 | Initiation of study treatment until disease progression (up to approximately 4 years) |
Countries
Australia, United States
Outcome results
None listed