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A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

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ClinicalTrials.gov Identifier: NCT03953235
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : November 28, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Gritstone Oncology, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Colorectal Cancer Pancreatic Cancer Solid Tumor Shared Neoantigen-Positive Solid Tumors Biological: GRT-C903 Biological: GRT-R904 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. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 18, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1
  • GRT-C903
  • GRT-R904
  • nivolumab
  • ipilimumab
Biological: GRT-C903
a shared neoantigen cancer vaccine prime

Biological: GRT-R904
a shared neoantigen cancer vaccine boost

Biological: nivolumab
anti-PD-1 monoclonal antibody

Biological: ipilimumab
anti-CTLA-4 monoclonal antibody

Experimental: Phase 2
  • GRT-C903
  • GRT-R904
  • nivolumab
  • ipilimumab
Biological: GRT-C903
a shared neoantigen cancer vaccine prime

Biological: GRT-R904
a shared neoantigen cancer vaccine boost

Biological: nivolumab
anti-PD-1 monoclonal antibody

Biological: ipilimumab
anti-CTLA-4 monoclonal antibody




Primary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Identify the recommended Phase 2 dose (RP2D) of GRT-C903 and GRT-R904 [ Time Frame: Up to approximately 6 months ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Duration of response (DOR) using RECIST v1.1 [ Time Frame: Initiation of study treatment until disease progression (up to approximately 27 months) ]
  4. Clinical benefit rate (CBR) using RECIST v1.1 [ Time Frame: Initiation of study treatment until disease progression (up to approximately 27 months) ]
  5. Progression-free survival (PFS) [ Time Frame: Up to approximately 4 years ]
  6. Overall survival (OS) [ Time Frame: Up to approximately 4 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or 2L 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, but have not initiated a new line of therapy
    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), but have not initiated a new line of therapy
    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, but have not initiated a new line of therapy
    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 in protocol, and is determined to express a HLA allele for antigen presentation of the identified tumor mutation
  • 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
  • Patient has received prior therapy consisting of anti-CTLA-4, anti-PD-1, anti-PD-L1, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, with the exception of patients with NSCLC or a mutation-positive solid tumor
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03953235


Contacts
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Contact: Andy Ferguson 857-327-9816 aferguson@gritstone.com
Contact: Cynthia Voong 510-871-6104 cvoong@gritstone.com

Locations
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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: New Patient Services    800-826-4673      
United States, Illinois
University of Chicago Medicine, Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Aurelie Desgardin       adesgard@medicine.bsd.uchicago.edu   
Contact       Phase1trials@medicine.bsd.uchicago.edu   
United States, New York
Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: David Manrique       dm3489@cumc.columbia.edu   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Dee McComb       davinia.mccomb@sarahcannon.com   
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Marcy Sullivan       marcy.sullivan@usoncology.com   
Sponsors and Collaborators
Gritstone Oncology, Inc.
Bristol-Myers Squibb

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Responsible Party: Gritstone Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03953235     History of Changes
Other Study ID Numbers: GO-005
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: November 28, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gritstone Oncology, Inc.:
neoantigen cancer vaccine
shared neoantigen
GRT-C903
GRT-R904
immunotherapy
PD-1
CTLA-4
nivolumab
ipilimumab
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Ipilimumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents