A Study of a Personalized Cancer Vaccine Targeting Shared Neoantigens

NCT03953235 | Completed Phase 1 FDA Drug

• 1 other identifier: GO-005
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 12

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. Based on the Phase 1 data, an updated vaccine candidate (SLATE-KRAS or version 2) was developed that removed 16 of the 20 mutations included in the original vaccine (version 1) and solely targets KRAS mutations.

Conditions

Non-Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Shared Neoantigen-Positive Solid Tumors

Keywords

neoantigen cancer vaccine; shared neoantigen; GRT-C903; GRT-R904; immunotherapy; PD-1; CTLA-4; nivolumab; ipilimumab

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs)

  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

  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

  Up to approximately 6 months

Secondary Outcomes (6)

• Measure the immune response to the neoantigens encoded by GRT-C903 and GRT-R904

  Baseline to end of treatment (up to approximately 12 months)

• Objective Response Rate (ORR) in Phase 1 using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 27 months)

• Duration of response (DOR) using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 27 months)

• Clinical benefit rate (CBR) using RECIST v1.1

  Initiation of study treatment until disease progression (up to approximately 27 months)

• Progression-free survival (PFS)

  Up to approximately 4 years

Study Arms (2)

Phase 1

EXPERIMENTAL

* GRT-C903 * GRT-R904 * nivolumab * ipilimumab

Biological: GRT-C903; Biological: GRT-R904; Biological: nivolumab; Biological: ipilimumab

Phase 2

EXPERIMENTAL

* GRT-C903 * GRT-R904 * nivolumab * ipilimumab Phase 2 for some patients includes a monthly or every two month treatment schedule

Biological: GRT-C903; Biological: GRT-R904; Biological: nivolumab; Biological: ipilimumab

Interventions

GRT-C903 BIOLOGICAL

a shared neoantigen cancer vaccine prime

Phase 1; Phase 2

GRT-R904 BIOLOGICAL

a shared neoantigen cancer vaccine boost

Phase 1; Phase 2

nivolumab BIOLOGICAL

anti-PD-1 monoclonal antibody

Phase 1; Phase 2

ipilimumab BIOLOGICAL

anti-CTLA-4 monoclonal antibody

Phase 1; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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 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 and have not received additional lines of systemic therapy in the metastatic setting.
• 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), and have not received additional lines of systemic therapy in the metastatic setting.
• 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 and have received no more than 1 prior line of therapy in the metastatic setting.
• 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 below, and is determined to express a HLA allele for antigen presentation of the identified tumor mutation:
• VERSION 1.0 of the expression cassette:
• BRAF\_G466V // CTNNB1\_S37F // CTNNB1\_S45F // CTNNB1\_S45P // CTNNB1\_T41A // ERBB2\_Y772\_A775dup // KRAS\_G12C or NRAS\_G12C // KRAS\_G12D or NRAS\_G12D // KRAS\_G12V // KRAS\_G13D // KRAS\_Q61H or NRAS\_Q61H // KRAS\_Q61K or NRAS\_Q61K // KRAS\_Q61L or NRAS\_Q61L // KRAS\_Q61R or NRAS\_Q61R // TP53\_K132E // TP53\_K132N // TP53\_R213L // TP53\_R249M // TP53\_S127Y
• VERSION 2.0 of the expression cassette:
• KRAS\_G12C or NRAS\_G12C // KRAS\_G12D or NRAS\_G12D // KRAS\_G12V or NRAS\_G12V // KRAS\_Q61H or NRAS\_Q61H
• 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)

You may not qualify if:

• Tumors with genetic characteristics as follows:
• For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK
• 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
• 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)

Sponsors & Collaborators

• Gritstone bio, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (12)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Chicago Medicine, Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Rappaport AR, Kyi C, Lane M, Hart MG, Johnson ML, Henick BS, Liao CY, Mahipal A, Shergill A, Spira AI, Goldman JW, Scallan CD, Schenk D, Palmer CD, Davis MJ, Kounlavouth S, Kemp L, Yang A, Li YJ, Likes M, Shen A, Boucher GR, Egorova M, Veres RL, Espinosa JA, Jaroslavsky JR, Kraemer Tardif LD, Acrebuche L, Puccia C, Sousa L, Zhou R, Bae K, Hecht JR, Carbone DP, Johnson B, Allen A, Ferguson AR, Jooss K. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results. Nat Med. 2024 Apr;30(4):1013-1022. doi: 10.1038/s41591-024-02851-9. Epub 2024 Mar 27.

  PMID: 38538867 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 16, 2019
• Study Start: July 18, 2019
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

US (12)