Description:
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.
Title
- Brief Title: A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens
- Official Title: A Phase 1/2 Study of GRT-C903/GRT-R904, a Vaccine Targeting Shared Neoantigens, in Combination With Immune Checkpoint Blockade for Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
GO-005
- NCT ID:
NCT03953235
Conditions
- Non Small Cell Lung Cancer
- Colorectal Cancer
- Pancreatic Cancer
- Solid Tumor
- Shared Neoantigen-Positive Solid Tumors
Interventions
Drug | Synonyms | Arms |
---|
GRT-C903 | | Phase 1 |
GRT-R904 | | Phase 1 |
nivolumab | | Phase 1 |
ipilimumab | | Phase 1 |
Purpose
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.
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. 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1 | Experimental | GRT-C903
GRT-R904
nivolumab
ipilimumab | - GRT-C903
- GRT-R904
- nivolumab
- ipilimumab
|
Phase 2 | Experimental | GRT-C903
GRT-R904
nivolumab
ipilimumab | - GRT-C903
- GRT-R904
- 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. Microsatellite-stable colorectal cancer (MSS-CRC) who are currently receiving
systemic treatment with a fluoropyrimidine and oxaliplatin and/or irinotecan that
may include a VEGF or EGFR targeting therapy as their 1L therapy for metastatic
disease OR who have experienced disease progression following treatment with a
fluoropyrimidine, oxaliplatin, and irinotecan that may include a VEGF or EGFR
targeting therapy and have not received additional lines of systemic therapy in
the metastatic setting.
2. Non-small cell lung cancer (NSCLC) who are currently receiving systemic treatment
with an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based
chemotherapy OR who have experienced disease progression following treatment with
an anti-PD-(L)1 antibody in combination with cytotoxic, platinum-based
chemotherapy (or anti-PD-(L)1 alone if patient refuses platinum-based
chemotherapy), and have not received additional lines of systemic therapy in the
metastatic setting.
3. Pancreatic ductal adenocarcinoma (PDA) who are currently receiving systemic
cytotoxic chemotherapy as their 1L therapy for metastatic disease OR who have
experienced disease progression on 1L systemic cytotoxic chemotherapy and have
received no more than 1 prior line of therapy in the metastatic setting.
4. Any solid tumor histology where the patient has experienced disease progression
with all available therapies known to confer clinical benefit
- Patient's tumor possesses one of the mutations listed below, and is determined to
express a HLA allele for antigen presentation of the identified tumor mutation:
BRAF_G466V // CTNNB1_S37F // CTNNB1_S45F // CTNNB1_S45P // CTNNB1_T41A //
ERBB2_Y772_A775dup // KRAS_G12C or NRAS_G12C // KRAS_G12D or NRAS_G12D // KRAS_G12V //
KRAS_G13D // KRAS_Q61H or NRAS_Q61H // KRAS_Q61K or NRAS_Q61K // KRAS_Q61L or NRAS_Q61L //
KRAS_Q61R or NRAS_Q61R // TP53_K132E // TP53_K132N // TP53_R213L // TP53_R249M //
TP53_S127Y
- ECOG Performance Status 0 or 1
- Measurable disease according to RECIST v1.1
- 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. Patients with known MSI-high disease based on institutional standard
- Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a
vaccination
- Bleeding disorder (eg., factor deficiency, coagulopathy) or history of significant
bruising or bleeding following IM injections or blood draws
- History of allogenic/solid organ transplant
- Active, known, or suspected autoimmune disease
- Active tuberculosis or recent (<2 week) clinically significant infection, or evidence
of active hepatitis B or hepatitis C
- Known history of positive test for human immunodeficiency (HIV) or known acquired
immunodeficiency syndrome (AIDS)
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 the neoantigens encoded by GRT-C903 and GRT-R904 |
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 27 months) |
Safety Issue: | |
Description: | |
Measure: | Duration of response (DOR) using RECIST v1.1 |
Time Frame: | Initiation of study treatment until disease progression (up to approximately 27 months) |
Safety Issue: | |
Description: | |
Measure: | Clinical benefit rate (CBR) using RECIST v1.1 |
Time Frame: | Initiation of study treatment until disease progression (up to approximately 27 months) |
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: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Gritstone Oncology, Inc. |
Trial Keywords
- neoantigen cancer vaccine
- shared neoantigen
- GRT-C903
- GRT-R904
- immunotherapy
- PD-1
- CTLA-4
- nivolumab
- ipilimumab
Last Updated
September 11, 2020