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A Study of a Personalized Neoantigen Cancer Vaccine

Primary Purpose

Non Small Cell Lung Cancer, Colorectal Cancer, Gastroesophageal Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GRT-C901
GRT-R902
nivolumab
ipilimumab
Sponsored by
Gritstone bio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring neoantigen cancer vaccine, personalized neoantigen cancer vaccine, GRT-C901, GRT-R902, immunotherapy, nivolumab, ipilimumab, PD-1, CTLA-4

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mayo Clinic Arizona
  • Mayo Clinic
  • The University of Chicago
  • Mayo Clinic
  • Memorial Sloan Kettering Cancer Center
  • Columbia University Medical Center
  • The Ohio State University Comprehensive Cancer Center
  • Tennessee Oncology
  • MD Anderson Cancer Center
  • Virginia Cancer Specialists
  • Peter MacCallum Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1

Phase 2 Cohorts

Arm Description

GRT-C901 GRT-R902 nivolumab ipilimumab

GRT-C901 GRT-R902 nivolumab ipilimumab

Outcomes

Primary Outcome Measures

Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Objective Response Rate (ORR) in Phase 2 using RECIST v1.1
Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902

Secondary Outcome Measures

Measure the immune response to neoantigens encoded by GRT-C901 and GRT-R902
Objective Response Rate (ORR) in Phase 1 using RECIST v1.1
Duration of response (DOR) using RECIST v1.1
Clinical benefit rate (using RECIST v1.1)
Progression-free survival (PFS)
Overall survival (OS)
Percentage of patients for whom vaccine is successfully manufactured and timeframe for vaccine manufacturing

Full Information

First Posted
August 6, 2018
Last Updated
September 11, 2023
Sponsor
Gritstone bio, Inc.
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03639714
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
February 13, 2019 (Actual)
Primary Completion Date
November 10, 2022 (Actual)
Study Completion Date
November 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gritstone bio, Inc.
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Colorectal Cancer, Gastroesophageal Adenocarcinoma, Urothelial Carcinoma
Keywords
neoantigen cancer vaccine, personalized neoantigen cancer vaccine, GRT-C901, GRT-R902, immunotherapy, nivolumab, ipilimumab, PD-1, CTLA-4

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1
Arm Type
Experimental
Arm Description
GRT-C901 GRT-R902 nivolumab ipilimumab
Arm Title
Phase 2 Cohorts
Arm Type
Experimental
Arm Description
GRT-C901 GRT-R902 nivolumab ipilimumab
Intervention Type
Biological
Intervention Name(s)
GRT-C901
Intervention Description
a patient-specific neoantigen cancer vaccine prime
Intervention Type
Biological
Intervention Name(s)
GRT-R902
Intervention Description
a patient-specific neoantigen cancer vaccine boost
Intervention Type
Biological
Intervention Name(s)
nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
anti-PD-1 monoclonal antibody
Intervention Type
Biological
Intervention Name(s)
ipilimumab
Other Intervention Name(s)
Yervoy
Intervention Description
anti-CTLA-4 monoclonal antibody
Primary Outcome Measure Information:
Title
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)
Title
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)
Title
Identify the recommended Phase 2 dose (RP2D) of GRT-C901 and GRT-R902
Time Frame
Up to approximately 6 months
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
Duration of response (DOR) using RECIST v1.1
Time Frame
Initiation of study treatment until disease progression (up to approximately 4 years)
Title
Clinical benefit rate (using RECIST v1.1)
Time Frame
Initiation of study treatment until disease progression (up to approximately 4 years)
Title
Progression-free survival (PFS)
Time Frame
Up to approximately 4 years
Title
Overall survival (OS)
Time Frame
Up to approximately 4 years
Title
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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) GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy 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: For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK For CRC and GEA, patients with known MSI-high disease based on institutional standard 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.
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
35970920
Citation
Palmer CD, Rappaport AR, Davis MJ, Hart MG, Scallan CD, Hong SJ, Gitlin L, Kraemer LD, Kounlavouth S, Yang A, Smith L, Schenk D, Skoberne M, Taquechel K, Marrali M, Jaroslavsky JR, Nganje CN, Maloney E, Zhou R, Navarro-Gomez D, Greene AC, Grotenbreg G, Greer R, Blair W, Cao MD, Chan S, Bae K, Spira AI, Roychowdhury S, Carbone DP, Henick BS, Drake CG, Solomon BJ, Ahn DH, Mahipal A, Maron SB, Johnson B, Rousseau R, Yelensky R, Liao CY, Catenacci DVT, Allen A, Ferguson AR, Jooss K. Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 2022 Aug;28(8):1619-1629. doi: 10.1038/s41591-022-01937-6. Epub 2022 Aug 15.
Results Reference
derived

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A Study of a Personalized Neoantigen Cancer Vaccine

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