Clinical Trials /

A Study of a Personalized Neoantigen Cancer Vaccine

NCT03639714

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Colorectal Carcinoma
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Non-Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of a Personalized Neoantigen Cancer Vaccine
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GO-004
  • NCT ID: NCT03639714

Conditions

  • Non Small Cell Lung Cancer
  • Colorectal Cancer
  • Gastroesophageal Adenocarcinoma
  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
GRT-C901Phase 1
GRT-R902Phase 1
nivolumabOpdivoPhase 1
ipilimumabYervoyPhase 1

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1ExperimentalGRT-C901 GRT-R902 nivolumab ipilimumab
  • GRT-C901
  • GRT-R902
  • nivolumab
  • ipilimumab
Phase 2 CohortsExperimentalGRT-C901 GRT-R902 nivolumab ipilimumab
  • GRT-C901
  • GRT-R902
  • 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. NSCLC who are planned for or have received no more than 1 cycle of systemic
                  treatment with cytotoxic, platinum-based chemotherapy

               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 MSI disease

               3. For CRC, patients with a known BRAF V600E mutation or patients with peritoneal
                  carcinomatosis

          -  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

          -  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 neoantigens encoded by GRT-C901 and GRT-R902
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 4 years)
Safety Issue:
Description:
Measure:Duration of response (DOR) using RECIST v1.1
Time Frame:Initiation of study treatment until disease progression (up to approximately 4 years)
Safety Issue:
Description:
Measure:Clinical benefit rate (using RECIST v1.1)
Time Frame:Initiation of study treatment until disease progression (up to approximately 4 years)
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:
Measure:Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing
Time Frame:Study enrollment to initiation of study treatment (up to approximately 6 months)
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
  • personalized neoantigen cancer vaccine
  • GRT-C901
  • GRT-R902
  • immunotherapy
  • nivolumab
  • ipilimumab
  • PD-1
  • CTLA-4

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