Clinical Trials /

A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

NCT03953235

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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 Tumors

Interventions

DrugSynonymsArms
GRT-C903Phase 1
GRT-R904Phase 1
anti-PD-(L)1Phase 1
anti-CTLA-4Phase 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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1ExperimentalGRT-C903 GRT-R904 anti-PD-(L)1 monoclonal antibody anti-CTLA-4 monoclonal antibody
  • GRT-C903
  • GRT-R904
  • anti-PD-(L)1
  • anti-CTLA-4
Phase 2ExperimentalGRT-C903 GRT-R904 anti-PD-(L)1 monoclonal antibody anti-CTLA-4 monoclonal antibody
  • GRT-C903
  • GRT-R904
  • anti-PD-(L)1
  • anti-CTLA-4

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

               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

               3. Pancreatic ductal adenocarcinoma (PDA) who are currently receiving systemic
                  cytotoxic chemotherapy

               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

        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:Not yet recruiting
Lead Sponsor:Gritstone Oncology, Inc.

Trial Keywords

  • neoantigen cancer vaccine
  • shared neoantigen
  • GRT-C903
  • GRT-R904
  • immunotherapy
  • PD-1
  • CTLA-4

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