Description:
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.
Title
- Brief Title: A Study of a Personalized Neoantigen Cancer Vaccine
- Official Title: An International Phase 1/2 Study of GRT-C901/GRT-R902, a Neoantigen Cancer Vaccine, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
GO-004
- NCT ID:
NCT03639714
Conditions
- Non Small Cell Lung Cancer
- Colorectal Cancer
- Gastroesophageal Adenocarcinoma
- Urothelial Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
GRT-C901 | | Phase 1 |
GRT-R902 | | Phase 1 |
nivolumab | Opdivo | Phase 1 |
ipilimumab | Yervoy | Phase 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 | Experimental | GRT-C901
GRT-R902
nivolumab
ipilimumab | - GRT-C901
- GRT-R902
- nivolumab
- ipilimumab
|
Phase 2 Cohorts | Experimental | GRT-C901
GRT-R902
nivolumab
ipilimumab | - GRT-C901
- GRT-R902
- nivolumab
- ipilimumab
|
Eligibility Criteria
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 exclusion criteria are listed in the clinical study protocol.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) using RECIST v1.1 |
Time Frame: | Initiation of study treatment until disease progression (up to approximately 4 years) |
Safety Issue: | |
Description: | |
Measure: | Clinical benefit rate (using RECIST v1.1) |
Time Frame: | Initiation of study treatment until disease progression (up to approximately 4 years) |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival (PFS) |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Overall survival (OS) |
Time Frame: | Up to approximately 4 years |
Safety Issue: | |
Description: | |
Measure: | Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing |
Time Frame: | Study enrollment to initiation of study treatment (up to approximately 6 months) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Gritstone Oncology, Inc. |
Trial Keywords
- neoantigen cancer vaccine
- personalized neoantigen cancer vaccine
- GRT-C901
- GRT-R902
- immunotherapy
- nivolumab
- ipilimumab
- PD-1
- CTLA-4
Last Updated
September 1, 2021