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A Study of a Personalized Neoantigen Cancer Vaccine

Sponsor
Gritstone bio, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03639714
Collaborator
Bristol-Myers Squibb (Industry)
214
Enrollment
11
Locations
2
Arms
48.5
Anticipated Duration (Months)
19.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: GRT-C901
  • Biological: GRT-R902
  • Biological: nivolumab
  • Biological: ipilimumab
 Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
214 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 13, 2019
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1

GRT-C901 GRT-R902 nivolumab ipilimumab

Biological: GRT-C901
a patient-specific neoantigen cancer vaccine prime

Biological: GRT-R902
a patient-specific neoantigen cancer vaccine boost

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Names:
  • Opdivo

    • Biological: ipilimumab
    anti-CTLA-4 monoclonal antibody
    Other Names:
  • Yervoy

    		•
    Experimental: Phase 2 Cohorts

    GRT-C901 GRT-R902 nivolumab ipilimumab

    Biological: GRT-C901
    a patient-specific neoantigen cancer vaccine prime

    Biological: GRT-R902
    a patient-specific neoantigen cancer vaccine boost

    Biological: nivolumab
    anti-PD-1 monoclonal antibody
    Other Names:
  • Opdivo

    • Biological: ipilimumab
    anti-CTLA-4 monoclonal antibody
    Other Names:
  • Yervoy

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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)]

    2. Objective Response Rate (ORR) in Phase 2 using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 27 months)]

    3. Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902 [Up to approximately 6 months]

    Secondary Outcome Measures

    1. Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902 [Baseline to end of treatment (up to approximately 12 months)]

    2. Objective Response Rate (ORR) in Phase 1 using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 4 years)]

    3. Duration of response (DOR) using RECIST v1.1 [Initiation of study treatment until disease progression (up to approximately 4 years)]

    4. Clinical benefit rate (using RECIST v1.1) [Initiation of study treatment until disease progression (up to approximately 4 years)]

    5. Progression-free survival (PFS) [Up to approximately 4 years]

    6. Overall survival (OS) [Up to approximately 4 years]

    7. 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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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 exclusion criteria are listed in the clinical study protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Arizona Phoenix Arizona United States 85054
    2 Mayo Clinic Jacksonville Florida United States 32224
    3 The University of Chicago Chicago Illinois United States 60637
    4 Mayo Clinic Rochester Minnesota United States 55905
    5 Memorial Sloan Kettering Cancer Center New York New York United States 10017
    6 Columbia University Medical Center New York New York United States 10032
    7 The Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    8 Tennessee Oncology Nashville Tennessee United States 37203
    9 MD Anderson Cancer Center Houston Texas United States 77030
    10 Virginia Cancer Specialists Fairfax Virginia United States 22031
    11 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000

    Sponsors and Collaborators

    • Gritstone bio, Inc.
    • Bristol-Myers Squibb

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gritstone bio, Inc.
    ClinicalTrials.gov Identifier:
    NCT03639714
    Other Study ID Numbers:
    • GO-004
    First Posted:
    Aug 21, 2018
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gritstone bio, Inc.
    neoantigen cancer vaccine
    personalized neoantigen cancer vaccine
    GRT-C901
    GRT-R902
    immunotherapy
    nivolumab
    ipilimumab
    PD-1
    CTLA-4
    Additional relevant MeSH terms:
    Adenocarcinoma
    Carcinoma, Transitional Cell
    Nivolumab
    Ipilimumab

    Study Results

    No Results Posted as of Sep 1, 2021