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A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03953235
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : December 26, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Gritstone Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 16, 2019
Last Update Posted Date December 26, 2019
Actual Study Start Date  ICMJE July 18, 2019
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • 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) ]
  • 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) ]
  • Identify the recommended Phase 2 dose (RP2D) of GRT-C903 and GRT-R904 [ Time Frame: Up to approximately 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03953235 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • 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) ]
  • 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) ]
  • Duration of response (DOR) using RECIST v1.1 [ Time Frame: Initiation of study treatment until disease progression (up to approximately 27 months) ]
  • Clinical benefit rate (CBR) using RECIST v1.1 [ Time Frame: Initiation of study treatment until disease progression (up to approximately 27 months) ]
  • Progression-free survival (PFS) [ Time Frame: Up to approximately 4 years ]
  • Overall survival (OS) [ Time Frame: Up to approximately 4 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Small Cell Lung Cancer
  • Colorectal Cancer
  • Pancreatic Cancer
  • Solid Tumor
  • Shared Neoantigen-Positive Solid Tumors
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Phase 1
    • GRT-C903
    • GRT-R904
    • nivolumab
    • ipilimumab
    Interventions:
    • Biological: GRT-C903
    • Biological: GRT-R904
    • Biological: nivolumab
    • Biological: ipilimumab
  • Experimental: Phase 2
    • GRT-C903
    • GRT-R904
    • nivolumab
    • ipilimumab
    Interventions:
    • Biological: GRT-C903
    • Biological: GRT-R904
    • Biological: nivolumab
    • Biological: ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andy Ferguson 857-327-9816 aferguson@gritstone.com
Contact: Cynthia Voong 510-871-6104 cvoong@gritstone.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03953235
Other Study ID Numbers  ICMJE GO-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gritstone Oncology, Inc.
Study Sponsor  ICMJE Gritstone Oncology, Inc.
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE Not Provided
PRS Account Gritstone Oncology, Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP